Dimethyl Sulfoxide → 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

HRID 932157Notes

Reaction equation

HRID 932157 reaction equation
C(Cl)(=O)C(Cl)=O.CS(C)=O.[Cl:11][C:12]1[CH:13]=[C:14]([C@@H:18]2[C@@H:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:22]([C@@H:31]([CH2:34][CH3:35])[CH2:32][OH:33])[C:21](=[O:36])[C@:20]([CH2:38][C:39]([OH:41])=[O:40])([CH3:37])[CH2:19]2)[CH:15]=[CH:16][CH:17]=1.C(N(CC)CC)C>ClCCl>[Cl:11][C:12]1[CH:13]=[C:14]([C@@H:18]2[C@@H:23]([C:24]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][CH:25]=3)[N:22]([C@@H:31]([CH2:34][CH3:35])[CH:32]=[O:33])[C:21](=[O:36])[C@:20]([CH2:38][C:39]([OH:41])=[O:40])([CH3:37])[CH2:19]2)[CH:15]=[CH:16][CH:17]=1

Participants

6

Reactant 4

HCID 679Dimethyl SulfoxideHCID 8471TriethylamineHCID 65578Oxalyl chlorideHCID 585738762-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Product 1

HCID 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

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a −78° C. solution of oxalyl chloride (0.166 mL, 0.332 mmol) in dichloromethane (2 mL) was added dimethylsulfoxide (0.047 mL, 0.663 mmol) dropwise. After ten minutes, 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (140 mg, 0.301 mmol; Example 185) in dichloromethane (2 mL) was added dropwise. After 15 minutes, triethylamine (0.210 mL, 1.507 mmol) was added dropwise. The mixture was warmed to 0° C. for 10 minutes and then quenched with 10% aq. citric acid. The mixture was diluted with water and extracted with dichloromethane (2×). The combined organic layers were washed with sat. aq. NaCl solution, dried over anhydrous Na2SO4, and concentrated to afford the title compound.

Workup

  1. waitAfter ten minutes
  2. customquenched with 10% aq. citric acid
  3. additionThe mixture was diluted with water
  4. extractionextracted with dichloromethane (2×)
  5. washThe combined organic layers were washed with sat. aq. NaCl solution
  6. dry with materialdried over anhydrous Na2SO4
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-bc737be460cd44a29f644e0e7f97788f
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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