Ethyl orthoformate → HCID 86586730, compound

HRID 2088187Notes

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.[CH2:39](OC(OCC)OCC)C.[N-:49]=[N+:50]=[N-:51].[Na+]>C(O)(=O)C>[CH2:10]([N:9]1[C@@H:3]2[C@H:2]([N:1]3[CH:39]=[N:51][N:50]=[N:49]3)[CH2:8][C@@:7]1([C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1)[C@H:6]([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)[CH2:5][CH2:4]2)[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

Conditions

Temperature: 90 °C

Procedure

(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; 209 mg, 0.39 mmol) in triethylorthoformate (3.5 ml, 19.22 mmol) and glacial acetic acid (1 ml) was heated to 90° C. Sodium azide (250 mg, 3.85 mmol) was added and the mixture further heated at 90° C. overnight. The mixture was cooled and partitioned between saturated sodium hydrogen carbonate solution and dichloromethane. The organics were dried (MgSO4) and concentrated in vacuo. The reaction mixture was purified by flash column chromatography [2.5% methanol in dichloromethane] to give the title compound as a cream-coloured foam (154 mg, 56%).

Workup

temperatureThe mixture was cooled
custompartitioned between saturated sodium hydrogen carbonate solution and dichloromethane
dry with materialThe organics were dried (MgSO4)
concentrationconcentrated in vacuo
customThe reaction mixture was purified by flash column chromatography [2.5% methanol in dichloromethane]

Sources & evidence

ORD record: ord-e091fa4206d447e7866d35ffd1b8abf5
Source dataset: uspto-grants-2004_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06727249B2

Reaction notes

Loading…