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

HRID 932164Notes

Reaction equation

HRID 932164 reaction equation
[O:1]1[CH2:4][C:3](=O)[CH2:2]1.[NH4+].[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:14]2[C@@H:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:18]([C@@H:27]([CH2:31][CH3:32])[CH2:28][NH:29][CH3:30])[C:17](=[O:33])[C@:16]([CH2:35][C:36]([O-:38])=[O:37])([CH3:34])[CH2:15]2)[CH:11]=[CH:12][CH:13]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl.CC(O)=O.CO>[Cl:7][C:8]1[CH:9]=[C:10]([C@@H:14]2[C@@H:19]([C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)[N:18]([C@@H:27]([CH2:31][CH3:32])[CH2:28][N:29]([CH3:30])[CH:3]3[CH2:2][O:1][CH2:4]3)[C:17](=[O:33])[C@:16]([CH2:35][C:36]([OH:38])=[O:37])([CH3:34])[CH2:15]2)[CH:11]=[CH:12][CH:13]=1

Participants

7

Reactant 3

HCID 5049666Sodium triacetoxyborohydride2×HCID 150242543-Oxetanone3×HCID 680009242-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(methylamino)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid-Ammonium Salt

Product 1

HCID 585732862-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(methyl(oxetan-3-yl)amino)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid

Reagents, catalysts & solvents 3

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolventHCID 887MethanolSolvent2×

Procedure

To a solution of oxetan-3-one (17.78 mg, 0.247 mmol) in DCE (3 mL) was added 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-1-(methylamino)butan-2-yl)-2-oxopiperidin-3-yl)acetic acid ammonium salt (61 mg, 0.123 mmol) obtained in Step A followed by sodium triacetoxyborohydride (78 mg, 0.370 mmol) and 3 drops AcOH. After 45 minutes, 3 ml MeOH and oxetan-3-one (12 mg, 0.17 mmol) were added. After stirring overnight, oxetan-3-one (12 mg, 0.17 mol) and sodium triacetoxyborohydride (60 mg, 0.32 mmol) were added. After 24 hours, the mixture was diluted with methanol and evaporated onto silica gel. The solid was purified by flash chromatography on silica gel (eluent: 0 to 100% [6:1:0.1 DCM/MeOH/NH4OH] in DCM). The product containing fractions were pooled, concentrated and repurified by preparative thin layer chromatography on silica gel (eluent: 10% MeOH/DCM) to afford the title compound.

Workup

  1. waitAfter 24 hours
  2. customevaporated onto silica gel
  3. customThe solid was purified by flash chromatography on silica gel (eluent: 0 to 100% [6:1:0.1 DCM/MeOH/NH4OH] in DCM)
  4. additionThe product containing fractions
  5. concentrationconcentrated
  6. customrepurified by preparative thin layer chromatography on silica gel (eluent: 10% MeOH/DCM)

Sources & evidence

ORD record
ord-1a3b0e65c61345fb87202d5c2237a524
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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