Ammonium Chloride → tert-Butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamate

HRID 1692282Notes

Reaction equation

HRID 1692282 reaction equation
[S:1]1[CH:5]=[C:4]([NH:6][C:7](=[O:13])[O:8][C:9]([CH3:12])([CH3:11])[CH3:10])[N:3]=[CH:2]1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[C:24]([C:26]1[CH:27]=[C:28]([S:33](Cl)(=[O:35])=[O:34])[CH:29]=[CH:30][C:31]=1[F:32])#[N:25].[Cl-].[NH4+]>O1CCCC1>[C:24]([C:26]1[CH:27]=[C:28]([S:33]([N:6]([C:4]2[N:3]=[CH:2][S:1][CH:5]=2)[C:7](=[O:13])[O:8][C:9]([CH3:10])([CH3:12])[CH3:11])(=[O:35])=[O:34])[CH:29]=[CH:30][C:31]=1[F:32])#[N:25]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 2733832Lithium HexamethyldisilazideHCID 27789083-Cyano-4-fluorobenzenesulfonyl chlorideHCID 53241636tert-butyl N-(1,3-thiazol-4-yl)carbamate

Product 1

HCID 59436569tert-Butyl [(3-cyano-4-fluorophenyl)sulfonyl]1,3-thiazol-4-ylcarbamateYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 1,3-thiazol-4-ylcarbamate (Preparation 72, 0.500 g, 0.002497 mol) in tetrahydrofuran (10.0 mL) was added lithium 1,1,1,3,3,3-hexamethyldisilazan-2-ide (1.0 M solution in tetrahydrofuran, 2.50 mL, 0.0025 mol) at 0° C. under nitrogen. After stirring for 1 hour at 0° C. the reaction mixture was cooled to −78° C. and 3-cyano-4-fluorobenzenesulfonyl chloride (0.453 g, 0.002063 mol) in tetrahydrofuran (5.0 mL) was added. The mixture was warmed to room temperature for 16 hours. Saturated aqueous ammonium chloride solution (20.0 mL) was added and the aqueous layer was extracted with ethyl acetate (3×20.0 mL). Combined organic layers were dried over sodium sulfate and concentrated in vacuo. This crude residue was purified using ISCO™ (12 g SiO2) eluting with ethyl acetate:dichloromethane (gradient 0:1 to 3:7, by volume) to afford the title compound as a white solid, 426 mg, 54% yield.

Workup

  1. temperaturewas cooled to −78° C.
  2. temperatureThe mixture was warmed to room temperature for 16 hours
  3. extractionthe aqueous layer was extracted with ethyl acetate (3×20.0 mL)
  4. dry with materialCombined organic layers were dried over sodium sulfate
  5. concentrationconcentrated in vacuo
  6. customThis crude residue was purified
  7. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-bfddb7655f3240b5ac5d5de575b7459b
Source dataset
uspto-grants-2012_04
Patent number
US08153814B2

Reaction notes

Loading…