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Stage #1: With lithium diisopropyl amide In tetrahydrofuran at -78℃;
Step 2 Compound [97] ( 1.0 g, 5.0 mmol) was dissolved in THF and cooled to -78 °C. Freshly prepared LDA (2. 1 eq.) was added to it and mixture was stirred for 1 h. (72-Bu)3SnCl ( 1.62 g, 5.0 mmol) was added dropwise and resulting mixture was stirred for 24 h. After completion of reaction 100 ml of aqueous saturated NH4CI was added and reaction was extracted with 3 X 100 ml EtOAc. The EtOAc layer was combined, washed with brine, dried over Na2S04 and concentrated to obtain compound [14] as brown solid (2.25 g, 92 percent yield). ESIMS: 491 (M+ + 1 )
65%
Stage #1: With n-butyllithium In tetrahydrofuran; hexanes at -78℃; Stage #2: at -78 - 20℃;
tert-Butyl 5-(tributylstannyl)thiazol-2-ylcarbamate: To a 500 mL round- bottomed flask was added tert-butyl thiazol-2-ylcarbamate (2.9 g, 14 mmol) and THF (200 mL). The solution was stirred at -78 0C and treated dropwise via addition funnel with n-butyllithium (2.5 M in hexanes (12 mL, 30 mmol, Aldrich)). The suspension was stirred at -78 0C for 30 minutes and was then treated dropwise via addition funnel with tributyltin chloride (4.3 mL, 16 mmol, Aldrich). The resulting pale yellow solution was stirred at -78 0C for 30 minutes, allowed to warm to room temperature, and then stirred for an additional 2.5 hours. The reaction was quenched with NH4Cl (100 mL). The layers were separated and the aqueous layer was extracted with ether (3 x 75 mL). The combined organic phases were washed with brine (100 mL), dried over MgSO4, filtered, and concentrated in vacuo to give a viscous oil mixed with a white solid. The product thus obtained was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep.(R). pre-packed silica gel column (40 g), eluting with a gradient of 10 to 20 percent EtOAc in hexane, to provide tert-butyl 5-(tributylstannyl)thiazol-2-ylcarbamate (4.6 g, 65 percent). LCMS (API-ES) m/z: 491 (M+H+).
With N-Bromosuccinimide; In tetrahydrofuran; at 20℃; for 12h;
tert-Butyl 5-bromothiazol-2-ylcarbamate 3. A suspension of NBS (6.2 g, 34.6 mmol, 1.1 equiv) and tert-butyl thiazol-2-ylcarbamate (6.3 g, 31.5 mmol, 1.0 equiv) in THF (100 mL) was stirred at room temperature for 12 hours. Then, the reaction mixture was filtrated and purified by column chromatography to give target compound (6.5 g, 73.9%).
With N-Bromosuccinimide; In tetrahydrofuran; at 20℃;
Terf-butyl 1 ,3-thiazol-2-ylcarbamate (90 g, 449.8 mmol, 1 eq.) is taken in THF (1 .4 L) to which is added /V-bromosuccinimide (88.06 g, 494.8 mmol, 1 .1 eq.) portion wise. The reaction mixture is then stirred at RT overnight. The reaction mass is concentrated to remove THF. The crude is purified by column chromatography to get the titled product.1H NMR(DMSO-d6, 400 MHz): delta 1 1 .73 (bs, 1 H), 7.42 (s, 1 H), 1.46 (s, 9H).
tert-butyl 5-((5-chloropyridin-3-yl)(hydroxy)methyl)thiazol-2-ylcarbamate[ No CAS ]
Yield
Reaction Conditions
Operation in experiment
55.4%
To a solution of ferf-butyl thiazol-2-ylcarbamate (1 .8 g, 9 mmol) in tetrahydrofuran (54 ml_) at -78 C was added n-butyllithium (7.9 ml_, 19.8 mmol) dropwise. Reaction was stirred for 1 h at -78 C for 1 h before a solution of <strong>[113118-82-4]5-chloronicotinaldehyde</strong> (1 .9 g, 13.5 mmol) in tetrahydrofuran (5 ml_) was added. Reaction mixture was warmed to room temperature over 2 h. The mixture was poured into ice water (50 ml_), pH was adjusted to 6-7 with aqueous 1 N hydrogen chloride and extracted with ethyl acetate (100 ml_ x 2). Combined organic layers were washed with brine (1 00 ml_), dried over sodium sulfate, filtered and concentrated. Purification by column chromatography (silica gel, petroleum ether/ethyl acetate = 1 :10-1 /2) affords ferf-butyl 5-((5-chloropyridin-3-yl)(hydroxy)methyl)thiazol-2-ylcarbamate (1 .7 g, 55.4%) as a white solid. LCMS (ESI) m/z: 342.1 [M+H]+.
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