Water → N-({1-[4-Hydroxy-4-(2-methanesulfinyl-thiazol-5-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

HRID 2096206Notes

Reaction equation

HRID 2096206 reaction equation
[OH:1][C:2]1([C:29]2[S:33][C:32]([S:34][CH3:35])=[N:31][CH:30]=2)[CH2:7][CH2:6][CH:5]([N:8]2[CH2:11][CH:10]([NH:12][C:13]([CH2:15][NH:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:27])([F:26])[F:25])[CH:19]=3)=[O:14])[CH2:9]2)[CH2:4][CH2:3]1.O.[OH:37]OS([O-])=O.[K+]>CO>[OH:1][C:2]1([C:29]2[S:33][C:32]([S:34]([CH3:35])=[O:37])=[N:31][CH:30]=2)[CH2:3][CH2:4][CH:5]([N:8]2[CH2:9][CH:10]([NH:12][C:13]([CH2:15][NH:16][C:17](=[O:28])[C:18]3[CH:23]=[CH:22][CH:21]=[C:20]([C:24]([F:25])([F:26])[F:27])[CH:19]=3)=[O:14])[CH2:11]2)[CH2:6][CH2:7]1

Participants

5

Reactant 3

HCID 962WaterHCID 23707502Potassium hydroxy sulfiteHCID 46240687N-({1-[4-Hydroxy-4-(2-methylsulfanyl-thiazol-5-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Product 1

HCID 46240688N-({1-[4-Hydroxy-4-(2-methanesulfinyl-thiazol-5-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

N-({1-[4-Hydroxy-4-(2-methylsulfanyl-thiazol-5-yl)-cyclohexyl]-azetidin-3-ylcarbamoyl}-methyl)-3-trifluoromethyl-benzamide (less polar isomer, 45a, 100 mg, 0.19 mmol) in MeOH (1 mL) and water (1 mL) was treated with OXONE (Aldrich, 230 mg, 0.38 mmol) at room temperature for 6 hours. The reaction mixture was partitioned between DCM and saturate NaHCO3. The organic layer was separated and the aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1, v/v). The combined organic layer was dried over anhydrous Na2SO4, filtered and concentrated to give the crude product, which was then purified by a CombiFlash® system using ethyl acetate and 7N NH3 in MeOH as eluent (from pure ethyl acetate to 5% 7N NH3 in MeOH in ethyl acetate) to afford the title compounds as a white solid.

Workup

  1. customThe reaction mixture was partitioned between DCM
  2. concentrationsaturate NaHCO3
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted 3 times with chloroform and IPA “cocktail” (˜3:1
  5. dry with materialThe combined organic layer was dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas then purified by a CombiFlash® system

Sources & evidence

ORD record
ord-3306f53a3b0648ecb11c05db3eac4cd4
Source dataset
uspto-grants-2013_05
Patent number
US08450304B2

Reaction notes

Loading…