Acetic Acid → HCID 86586725, compound

HRID 2088189Notes

Reaction equation

[NH2:1][C@@H:2]1[CH2:8][C@:7]2([C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[N:9]([CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C@H:3]1[CH2:4][CH2:5][C@H:6]2[O:23][CH2:24][C:25]1[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=1.[N-]=[N+]=[N-].[Na+].[C:43](O)(=[O:45])[CH3:44]>C(OC(OCC)OCC)C>[C:43]([NH:1][C@@H:2]1[CH2:8][C@:7]2([C:17]3[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=3)[N:9]([CH2:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)[C@H:3]1[CH2:4][CH2:5][C@H:6]2[O:23][CH2:24][C:25]1[CH:26]=[C:27]([C:35]([F:38])([F:36])[F:37])[CH:28]=[C:29]([C:31]([F:32])([F:33])[F:34])[CH:30]=1)(=[O:45])[CH3:44]

Participants

Conditions

Temperature: 90 °C

Procedure

To (1R*,2R*,5S*,6R*)-6-amino-8-benzyl-2-{[3,5-bis(trifluoromethyl)phenyl]methoxy}-1-phenyl-8-azabicyclo[3.2.1]octane (Example 108; 256 mg, 0.48 mmol) and sodium azide (75 mg, 1.15 mmol) in triethylorthoformate (0.25 ml) was added glacial acetic acid (2.5 ml) and the reaction mixture heated at 90° C. for 3 hours. The reaction mixture was cooled then concentrated in vacuo and partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organics were dried (MgSO4) and concentrated in vacuo to give a brown oil. This was purified by flash column chromatography [5% methanol in dichloromethane] to give the title compound (66 mg, 24%).

Workup

temperatureThe reaction mixture was cooled
concentrationthen concentrated in vacuo
custompartitioned between saturated sodium hydrogen carbonate solution and dichloromethane
dry with materialThe organics were dried (MgSO4)
concentrationconcentrated in vacuo
customto give a brown oil
customThis was purified by flash column chromatography [5% methanol in dichloromethane]

Sources & evidence

ORD record: ord-f0d5b90445c14a2f933e9983f1b94808
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06727249B2

Reaction notes

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