Sodium triacetoxyborohydride → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)butan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

HRID 932162Notes

Reaction equation

HRID 932162 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH:22]=O)[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Cl.[F:33][C:34]([F:41])([F:40])[C:35]1([OH:39])[CH2:38][NH:37][CH2:36]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:24][CH3:25])[CH2:22][N:37]3[CH2:38][C:35]([OH:39])([C:34]([F:41])([F:40])[F:33])[CH2:36]3)[C:11](=[O:26])[C@:10]([CH2:28][C:29]([OH:31])=[O:30])([CH3:27])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 467351523-(Trifluoromethyl)azetidin-3-ol hydrochlorideHCID 585738802-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-oxobutan-2-yl)piperidin-3-yl)acetic acid

Product 1

HCID 585734862-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(3-hydroxy-3-(trifluoromethyl)azetidin-1-yl)butan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxo-1-((S)-1-oxobutan-2-yl)piperidin-3-yl)acetic acid (70 mg, 0.151 mmol; Example 210, Step A) in DCE (3 mL) was added 53.8 mg (0.303 mmol) of 3-(trifluoromethyl)azetidin-3-ol hydrochloride (U.S. patent application publication no 2007/0275930) and sodium triacetoxyborohydride (64.2 mg, 0.303 mmol). After stirring for 18 hours, the mixture was partitioned between water and DCM. The aqueous layer was washed with DCM. The combined organic layers were washed with sat. aq. NaCl solution, dried over anhydrous Na2SO4, filtered and the filtrate was concentrated. The residue was purified by preparative thin layer chromatography on silica gel (eluent: 50% ethyl acetate/hexanes) to afford the title compound.

Workup

  1. customthe mixture was partitioned between water and DCM
  2. washThe aqueous layer was washed with DCM
  3. washThe combined organic layers were washed with sat. aq. NaCl solution
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by preparative thin layer chromatography on silica gel (eluent: 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-e08a852d84c14e709bff3661d51ff692
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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