Acetic Acid → HCID 67999092, compound

HRID 932156Notes

Reaction equation

HRID 932156 reaction equation
[CH2:1]([C@@:4]1([CH3:30])[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@@H:31]12[CH2:37][C@@H:34]([NH:35][CH2:36]1)[CH2:33][O:32]2.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(O)(=O)C>ClCCCl>[C@@H:31]12[CH2:37][C@@H:34]([N:35]([CH2:25][C@@H:24]([N:6]3[C@H:7]([C:17]4[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][CH:18]=4)[C@@H:8]([C:10]4[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=4)[CH2:9][C@@:4]([CH2:1][CH:2]=[CH2:3])([CH3:30])[C:5]3=[O:29])[CH2:27][CH3:28])[CH2:36]1)[CH2:33][O:32]2

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 5049666Sodium triacetoxyborohydrideHCID 42554306(1R,4R)-2-Oxa-5-azabicyclo[2.2.1]heptaneHCID 58573909(S)-2-((3S,5R,6S)-3-Allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal

Product 1

HCID 67999092HCID 67999092, compound

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of (S)-2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanal (100 mg, 0.224 mmol; Example 91, Step C) in DCE (2 mL) was added (1R,4R)-2-oxa-5-azabicyclo[2.2.1]heptane (Butora, G.; Goble, S.; Pastemak, A.; Yang, L.; Zhou, C.; Moyes, C. U.S. Patent Publication No. 2008/0081803 (50 mg, 0.504 mmol) followed by sodium triacetoxyborohydride (95 mg, 0.448 mmol) and acetic acid (1.2 μL, 0.022 mmol). After stirring overnight, the mixture was quenched with sat. aq. NaHCO3 solution. The mixture was extracted with ethyl acetate (2×). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography on silica gel (eluent: 1 to 5% methanol/dichloromethane) to afford the title compound.

Workup

  1. customthe mixture was quenched with sat. aq. NaHCO3 solution
  2. extractionThe mixture was extracted with ethyl acetate (2×)
  3. washThe combined organic layers were washed with sat. aq. NaCl solution
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography on silica gel (eluent: 1 to 5% methanol/dichloromethane)

Sources & evidence

ORD record
ord-b9ef9ada479c4e3186e7844efc006252
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

Loading…