Ethyl Acetate → HCID 67812581, compound

HRID 2401369Notes

Reaction equation

HRID 2401369 reaction equation
[Cl-].[C:2]([O:6][C:7](=[O:10])[CH2:8][Zn+])([CH3:5])([CH3:4])[CH3:3].[Cl:11][C:12]1[CH:40]=[CH:39][C:15]([C:16]([C:18]2[C:22]([CH3:23])=[C:21]([CH3:24])[S:20][C:19]=2[C:25]2[C:26]([CH3:38])=[N:27][O:28][C:29]=2/[CH:30]=[N:31]/[S@@:32]([C:34]([CH3:37])([CH3:36])[CH3:35])=[O:33])=[O:17])=[CH:14][CH:13]=1.[NH4+].[Cl-].CCOC(C)=O>C1COCC1>[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]([C:18]2[C:22]([CH3:23])=[C:21]([CH3:24])[S:20][C:19]=2[C:25]2[C:26]([CH3:38])=[N:27][O:28][C:29]=2[C@H:30]([NH:31][S@@:32]([C:34]([CH3:35])([CH3:36])[CH3:37])=[O:33])[CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:10])=[O:17])=[CH:39][CH:40]=1.[Cl:11][C:12]1[CH:13]=[CH:14][C:15]([C:16]([C:18]2[C:22]([CH3:23])=[C:21]([CH3:24])[S:20][C:19]=2[C:25]2[C:26]([CH3:38])=[N:27][O:28][C:29]=2[C@@H:30]([NH:31][S@@:32]([C:34]([CH3:35])([CH3:36])[CH3:37])=[O:33])[CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:4])[CH3:3])=[O:10])=[O:17])=[CH:39][CH:40]=1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 88439818HCID 88439818, compoundHCID 178451183HCID 178451183, compound2×

Product 2

HCID 67812581HCID 67812581, compoundYield 43%HCID 67813784HCID 67813784, compoundYield 31%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C.) solution of (2-tert-butoxy-2-oxoethyl)zinc(II) chloride (0.200 mL, 0.100 mmol) was added a solution of (R,E)-N-((4-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)-3-methylisoxazol-5-yl)methylene)-2-methylpropane-2-sulfinamide (0.039 g, 0.084 mmol) in THF (0.5 mL). Additional THF (2×0.5 mL) was used to aid in complete transfer of the sulfinamide. After 1.5 h, additional (2-tert-butoxy-2-oxoethyl)zinc(II) chloride (1.00 mL, 0.500 mmol) was added and the reaction temperature was allowed to reach to ambient temperatures. After several hours, the reaction mixture was diluted aqueous saturated NH4Cl and EtOAc. The aqueous layer was extracted with EtOAc (2×), the combined organic phase was washed with water (2×), dried over Na2SO4 and concentrated in vacuo to give a thick oil. The resultant oil was purified on Biotage system (gradient elution, 12% MTBE:95% Hexanes to 100% MTBE) to deliver the (3R)-tert-butyl 3-(4-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)-3-methylisoxazol-5-yl)-3-((R)-1,1-dimethylethylsulfinamido)propanoate (0.016 g, 0.027 mmol, 31% yield) as a light white foam and (3S)-tert-butyl 3-(4-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)-3-methylisoxazol-5-yl)-3-((R)-1,1-dimethylethylsulfinamido)propanoate (0.021 g, 0.036 mmol, 43% yield) as a light white foam. (3R)-tert-butyl 3-(4-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)-3-methylisoxazol-5-yl)-3-((R)-1,1-dimethylethylsulfinamido)propanoate: LC/MS m/z 579 [(M (35Cl)+H]+ and m/z 581 [(M (37Cl)+H]+ and (3S)-tert-butyl 3-(4-(3-(4-chlorobenzoyl)-4,5-dimethylthiophen-2-yl)-3-methylisoxazol-5-yl)-3-((R)-1,1-dimethylethylsulfinamido)propanoate: LC/MS m/z 579 [M+H]+.

Workup

  1. waitAfter several hours
  2. extractionThe aqueous layer was extracted with EtOAc (2×)
  3. washthe combined organic phase was washed with water (2×)
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customto give a thick oil
  7. customThe resultant oil was purified on Biotage system (gradient elution, 12% MTBE:95% Hexanes to 100% MTBE)

Sources & evidence

ORD record
ord-bbd7d917029e4278a2441dfab5b5690d
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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