Acetic Acid → (3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(1-(methylamino)butan-2-yl)piperidin-2-one

HRID 932063Notes

Reaction equation

HRID 932063 reaction equation
[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=2)[N:6]([C@@H:24]([CH2:27][CH3:28])[CH:25]=O)[C:5]1=[O:29])[CH:2]=[CH2:3].C(O)(=O)C.[CH3:34][NH2:35].C1COCC1>ClCCCl>[CH2:1]([C@@H:4]1[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([CH:24]([CH2:27][CH3:28])[CH2:25][NH:35][CH3:34])[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 8028TetrahydrofuranHCID 86660727(S)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanal

Product 1

HCID 68000418(3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(1-(methylamino)butan-2-yl)piperidin-2-one

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 1.67 g (3.88 mmol) of (S)-2-((3R,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-2-oxopiperidin-1-yl)butanal (Example 126, Step C) and acetic acid (6.60 mL, 116 mmol) in DCE (40 mL) was added 2 M methylamine in THF (19.40 mL, 38.8 mmol) and sodium triacetoxy hydroborate (3.29 g, 15.52 mmol) at room temperature. The reaction was stirred for 2 days. The reaction was quenched with sat aq. NaHCO3, extracted with EtOAc, and the combined organic layers were washed with 1N NaOH and sat. aq. NaCl solution, dried over Na2SO4 and concentrated under reduced pressure to provide the title compound as a pale yellow oil, which was used without further purification in the next step.

Workup

  1. customThe reaction was quenched with sat aq. NaHCO3
  2. extractionextracted with EtOAc
  3. washthe combined organic layers were washed with 1N NaOH and sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c487c93867fa408bbe55f2edffd3d621
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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