Citric Acid → HCID 178516685, compound

HRID 931931Notes

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]#[N:28])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl-].[NH4+].[N-:31]=[N+:32]=[N-:33].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[NH:31]1[C:27]([CH2:26][C@H:10]2[CH2:9][C@H:8]([C:4]3[CH:5]=[CH:6][CH:7]=[C:2]([Cl:1])[CH:3]=3)[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[CH2:23][CH2:24]3)[C:11]2=[O:25])=[N:28][N:33]=[N:32]1

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 136 mg (0.33 mmol) of 2-((3R,5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-(cyclopropylmethyl)-2-oxopiperidin-3-yl)acetonitrile (Example 55, Step A) in 1.8 mL of DMF was added ammonium chloride (176 mg, 3290 μmol) and sodium azide (214 mg, 3290 μmol). The resulting mixture was stirred at 90° C. for 4 days. Then, the reaction was acidified (aq. 10% citric acid) and extracted (2×EtOAc). The combined organic layers were washed with sat. aq. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Separation by reversed phase HPLC (60-90% AcCN/H2O in 30 min) provided the title compound as a white solid.

Workup

extractionextracted (2×EtOAc)
washThe combined organic layers were washed with sat. aq. NaCl solution
dry with materialdried over Na2SO4
filtrationfiltered
concentrationthe filtrate was concentrated under reduced pressure
customSeparation by reversed phase HPLC (60-90% AcCN/H2O in 30 min)

Sources & evidence

ORD record: ord-959a083d6a6c43369a0e1c56d1d3f731
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296736B2

Reaction notes

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