Trifluoroacetic acid → 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoic acid

HRID 932004Notes

Reaction equation

[CH2:1]([C@@:4]1([CH3:35])[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]([CH2:32][CH3:33])[C:25]([O:27]C(C)(C)C)=[O:26])[C:5]1=[O:34])[CH:2]=[CH2:3].C1(OC)C=CC=CC=1.C(O)(C(F)(F)F)=O>CCOCC>[CH2:1]([C@@:4]1([CH3:35])[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]([CH2:32][CH3:33])[C:25]([OH:27])=[O:26])[C:5]1=[O:34])[CH:2]=[CH2:3]

Participants

Conditions

Temperature: 0 °C

Procedure

To a 15-mL round-bottomed flask was added (S)-tert-butyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-2-oxopiperidin-1-yl)butanoate (420 mg, 0.813 mmol) (Example 1, Step F) and anisole (444 μL, 4.07 mmol), followed by TFA (4066 μL) which had been pre-cooled to 0° C. The reaction mixture was stirred at 0° C. for 1 h, diluted with 50 ml of ether, and the combined organics were washed with 20 ml water, NaHCO3/sat NaCl solution until neutral, then dried over Na2SO4, filtered and the filtrate was concentrated. Purification of the residue by flash chromatography on silica gel (eluent: 0 to 20% EtOAc/hexanes, gradient elution) provided the title compound.

Workup

washthe combined organics were washed with 20 ml water, NaHCO3/
dry with materialthen dried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated
customPurification of the residue by flash chromatography on silica gel (eluent: 0 to 20% EtOAc/hexanes, gradient elution)

Sources & evidence

ORD record: ord-b9de0e0ddaa84c5a96c8c00074829150
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296736B2

Reaction notes

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