Thiazole → 2-Methyl-propane-2-sulfinic acid (3-thiazol-2-yl-oxetan-3-yl)-amide

HRID 927724Notes

Reaction equation

HRID 927724 reaction equation
C([Li])CCC.[S:6]1[CH:10]=[CH:9][N:8]=[CH:7]1.[CH3:11][C:12]([S:15]([N:17]=[C:18]1[CH2:21][O:20][CH2:19]1)=[O:16])([CH3:14])[CH3:13]>O1CCCC1>[S:6]1[CH:10]=[CH:9][N:8]=[C:7]1[C:18]1([NH:17][S:15]([C:12]([CH3:14])([CH3:13])[CH3:11])=[O:16])[CH2:21][O:20][CH2:19]1

Participants

5

Reactant 3

HCID 9256ThiazoleHCID 468399952-Methyl-N-(oxetan-3-ylidene)propane-2-sulfinamideHCID 178418339Butyllithium

Product 1

HCID 711130582-Methyl-propane-2-sulfinic acid (3-thiazol-2-yl-oxetan-3-yl)-amideYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

A solution of n-butyllithium in hexanes (1.6 M, 2.5 mL, 3.99 mmol) was added dropwise to a solution of thiazole (364 mg, 4.23 mmol) in tetrahydrofuran (30 mL) at −78° C. The resulting mixture was stirred for 30 min at −78° C. before a solution of 2-methyl-n-(oxetan-3-ylidene)propane-2-sulfinamide (CAN 1158098-73-7) (500 mg, 2.85 mmol) in tetrahydrofuran (3.5 mL) was added dropwise at −78° C. The reaction solution was stirred for an additional 30 min at −78° C. before being warmed to 22° C., and then was quenched with saturated aqueous ammonium chloride solution. The crude reaction mixture was then partitioned between water and ethyl acetate. The aqueous layer was further extracted with ethyl acetate and the organic layers were combined. The combined layers were washed with saturated aqueous sodium chloride solution, and the washed solution was dried with anhydrous sodium sulfate and evaporated down to dryness. The crude product was purified by flash-column chromatography (40% ethyl acetate-hexanes, grading to 100% ethyl acetate, then flushing with 10% methanol-dichloromethane) to give the title compound (495 mg, 67%). MS (EI): m/e=261.0 [M+H]+.

Workup

  1. additionwas added dropwise at −78° C
  2. temperaturebefore being warmed to 22° C.
  3. customwas quenched with saturated aqueous ammonium chloride solution
  4. customThe crude reaction mixture
  5. customwas then partitioned between water and ethyl acetate
  6. extractionThe aqueous layer was further extracted with ethyl acetate
  7. washThe combined layers were washed with saturated aqueous sodium chloride solution
  8. dry with materialthe washed solution was dried with anhydrous sodium sulfate
  9. customevaporated down to dryness
  10. customThe crude product was purified by flash-column chromatography (40% ethyl acetate-hexanes
  11. customflushing with 10% methanol-dichloromethane)

Sources & evidence

ORD record
ord-1710c8da19c44234958897e5cf4dc3c9
Source dataset
uspto-grants-2016_03
Patent number
US09290451B2

Reaction notes

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