tert-Butanol → HCID 19691237, compound
Reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:15][CH2:14][C:13]([CH2:19][F:20])(C(O)=O)[CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([N:23]([CH2:26]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:35])C=CC=CC=1.[CH3:45][C:46]([OH:49])([CH3:48])[CH3:47]>>[C:46]([O:49][C:26]([NH:23][C:13]1([CH2:19][F:20])[CH2:14][CH2:15][N:11]([C:9]([O:8][CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)=[O:10])[CH2:12]1)=[O:35])([CH3:48])([CH3:47])[CH3:45]Participants
Procedure
To a solution of 1-(benzyloxycarbonyl)-3-(fluoromethyl)pyrrolidine-3-carboxylic acid (2.77 g, 9.85 mmol) in anhydrous t-BuOH (30 mL) was added triethylamine (6.86 mL, 49.24 mmol) and diphenyl phosphoryl azide (3.29 mL, 14.77 mmol). The mixture was heated at reflux for 16 hours under a nitrogen atmosphere. The mixture was cooled to ambient temperature, and partitioned between diethyl ether and water. The organic layer was separated and washed with saturated sodium bicarbonate solution and brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by column chromatography (Biotage 40M, 20% ethyl acetate/hexanes) to afford benzyl 3-(tert-butoxycarbonylamino)-3-(fluoromethyl)pyrrolidine-1-carboxylate (2.27 g, 65%).
Workup
- temperatureThe mixture was heated
- temperatureat reflux for 16 hours under a nitrogen atmosphere
- custompartitioned between diethyl ether and water
- customThe organic layer was separated
- washwashed with saturated sodium bicarbonate solution and brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated under reduced pressure
- customThe residue was purified by column chromatography (Biotage 40M, 20% ethyl acetate/hexanes)
Sources & evidence
- ORD record
- ord-34ca27b59597488f98b8ee9f7bd6d327
- Source dataset
- uspto-grants-2014_11
- Patent number
- US08889704B2
Reaction notes
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