Triphenylphosphine → (+)-(3R,4R)-4-(4-Fluoro-phenyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester
Reaction equation
[C:1]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O.[C:32]([O:36][C:37]([N:39]1[CH2:44][CH2:43][C@@H:42]([C:45]2[CH:50]=[CH:49][C:48]([F:51])=[CH:47][CH:46]=2)[C@@H:41]([C:52]([OH:54])=[O:53])[CH2:40]1)=[O:38])([CH3:35])([CH3:34])[CH3:33]>O1CCCC1>[CH3:1][O:53][C:52]([C@@H:41]1[C@H:42]([C:45]2[CH:46]=[CH:47][C:48]([F:51])=[CH:49][CH:50]=2)[CH2:43][CH2:44][N:39]([C:37]([O:36][C:32]([CH3:35])([CH3:33])[CH3:34])=[O:38])[CH2:40]1)=[O:54]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Procedure
To a solution of triphenylphosphine (3.82 g, 14.6 mmol) in 70 ml tetrahydrofuran was added diethyl azodicarboxylate (2.53 g, 14.6 mmol) at 0° C. After 30′ methanol (4.55 ml, 112.0 mmol) and a solution of (+)-(3R,4R)-4-(4-fluoro-phenyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (3.62 g, 11.2 mmol, 93.6% ee) in 30 ml tetrahydrofuran were added subsequently at 0-5° C. The reaction mixture was stirred for 20 h at room temperature. Quenching with water was followed by extraction with tert-butyl methyl ether (3×100 ml). The combined organic layers were dried over sodium sulfate, concentrated under reduced pressure and purified by flash chromatography (n-heptane/ethyl acetate) to give the title compound (3.55 g, 94%) as a colorless oil.
Workup
- customQuenching with water
- extractionwas followed by extraction with tert-butyl methyl ether (3×100 ml)
- dry with materialThe combined organic layers were dried over sodium sulfate
- concentrationconcentrated under reduced pressure
- custompurified by flash chromatography (n-heptane/ethyl acetate)
Sources & evidence
- ORD record
- ord-011f84c210d4489bb1d73bd28f6f03d1
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08580821B2
Reaction notes
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