Ammonia → 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetamide

HRID 931925Notes

Reaction equation

[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([CH2:21][CH:22]3[CH2:24][CH2:23]3)[C:11](=[O:25])[C@@H:10]([CH2:26][C:27](OC)=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[NH3:31].CO.[C-]#N.[Na+]>>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:15]=[CH:16][C:17]([Cl:20])=[CH:18][CH:19]=3)[N:12]([CH2:21][CH:22]3[CH2:23][CH2:24]3)[C:11](=[O:25])[C@@H:10]([CH2:26][C:27]([NH2:31])=[O:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

Reactant 4

HCID 222Ammonia

HCID 887Methanol

HCID 8929Sodium Cyanide

HCID 56591325Methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetate

Product 1

HCID 565912182-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetamide

Conditions

Temperature: 50 °C

Procedure

In a sealed tube, 60 mg (134 μmol) of methyl 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetate (Example 47) and 4.8 mL of a solution of ammonia in methanol (7N, 3.4 mmol) were stirred at 25° C. for 5 days. Then NaCN (3 mg) was added and the resulting solution was stirred at 50° C. for 3 days. Excess NH3 and MeOH were removed under reduced pressure. Separation by reversed phase HPLC (10 to 90% AcCN/H2O in 45 min) provided the title compound as a a white solid.

Workup

customExcess NH3 and MeOH were removed under reduced pressure
customSeparation by reversed phase HPLC (10 to 90% AcCN/H2O in 45 min)

Sources & evidence

ORD record: ord-2f0876427c684f5a9419f72e3cfc7281
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296736B2

Reaction notes

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