1-Chloroethyl chloroformate → 3-[2-(Trifluoromethyl)-4'-(difluoromethoxy)benzhydryloxy]azetidine hydrochloride
Reaction equation
C([N:14]1[CH2:17][CH:16]([O:18][CH:19]([C:30]2[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:39])[F:38])=[CH:32][CH:31]=2)[C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=2[C:26]([F:29])([F:28])[F:27])[CH2:15]1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cl:40]C(OC(Cl)C)=O>C(Cl)Cl>[ClH:40].[F:29][C:26]([F:27])([F:28])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][C:20]=1[CH:19]([O:18][CH:16]1[CH2:17][NH:14][CH2:15]1)[C:30]1[CH:35]=[CH:34][C:33]([O:36][CH:37]([F:38])[F:39])=[CH:32][CH:31]=1Participants
4
Reactant 2
Product 1
Reagents, catalysts & solvents 1
Procedure
To a stirred solution of 1-benzhydryl-3-[2-(trifluoromethyl)-4′-(difluoro-methoxy)benzhydryloxy]azetidine (174) (2.73 g from previous step-assumed 4.7 mmol) in DCM (40 mL), cooled in ice-water bath, was added 1-chloroethyl chloroformate (1 mL, 9.4 mmol). After 1 h, the mixture was allowed to warm to ambient temperature. After a further 5.5 h, the mixture was concentrated under reduced pressure, methanol (40 mL) was added, and the mixture was stirred for 16 h. The mixture was concentrated under reduced pressure, then dissolved in iso-hexane (4 mL)-DIPE (30 mL)-MeOH (2 mL). Upon stirring, a precipitate formed. The mixture was cooled in ice-water bath for 15 min.
Workup
- waitAfter a further 5.5 h
- concentrationthe mixture was concentrated under reduced pressure, methanol (40 mL)
- additionwas added
- concentrationThe mixture was concentrated under reduced pressure
- dissolutiondissolved in iso-hexane (4 mL)-DIPE (30 mL)-MeOH (2 mL)
- stirringUpon stirring
- customa precipitate formed
Sources & evidence
- ORD record
- ord-50c20bd30b5747c1b945b789e9d83ef9
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07504522B2
Reaction notes
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