Diethyl Ether → Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetate

HRID 1048448Notes

Reaction equation

HRID 1048448 reaction equation
[Si]([O:18][CH2:19][C@@H:20]([N:23]1[C@H:28]([C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=2)[C@@H:27]([C:36]2[CH:41]=[CH:40][CH:39]=[C:38]([Cl:42])[CH:37]=2)[CH2:26][C@@:25]([CH2:44][C:45]([OH:47])=[O:46])([CH3:43])[C:24]1=[O:48])[CH2:21][CH3:22])(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[CH3:49][Si](C=[N+]=[N-])(C)C.C(OCC)C.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CO.C1C=CC=CC=1.C1COCC1>[Cl:42][C:38]1[CH:37]=[C:36]([C@@H:27]2[C@@H:28]([C:29]3[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][CH:30]=3)[N:23]([C@@H:20]([CH2:21][CH3:22])[CH2:19][OH:18])[C:24](=[O:48])[C@:25]([CH2:44][C:45]([O:47][CH3:49])=[O:46])([CH3:43])[CH2:26]2)[CH:41]=[CH:40][CH:39]=1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 167693TrimethylsilyldiazomethaneHCID 2724141Tetrabutylammonium FluorideHCID 601541832-((3R,5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid

Product 1

HCID 58573771Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-hydroxybutan-2-yl)-3-methyl-2-oxopiperidin-3-yl)acetate

Reagents, catalysts & solvents 3

HCID 241BenzeneSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of 2-((3R,5R,6S)-1-((S)-1-(tert-butyldiphenylsilyloxy)butan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-3-yl)acetic acid (Example 185) in MeOH (2 mL) and benzene (8 mL) was stirred with (trimethylsilyl)diazomethane, 2.0 M in diethyl ether (2.02 mL, 4.04 mmol) at rt for 0.5 h. After that time the mixture was concentrated to give the crude methyl ester, which was treated with TBAF in THF at rt for 30 h. The mixture was concentrated and purified by chromatography on silica gel (0 to 100% EtOAc in hexanes) to give the title compound. Mass Spectrum (ESI) m/z=478 (M+1).

Workup

  1. concentrationAfter that time the mixture was concentrated
  2. customto give the crude methyl ester, which
  3. concentrationThe mixture was concentrated
  4. custompurified by chromatography on silica gel (0 to 100% EtOAc in hexanes)

Sources & evidence

ORD record
ord-5043a48901c0476f94b5c67808538100
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

Loading…