Benzyl Alcohol → 3-Benzyloxycarbonylamino-3-(1,1-difluoro-allyl)-piperidine-1-carboxylic acid tert-butyl ester

HRID 1912416Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:17]([F:21])([F:20])[CH:18]=[CH2:19])(C(O)=O)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([N:24]([CH2:27]C)CC)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:36])C=CC=CC=1.[CH2:46]([OH:53])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1>C1(C)C=CC=CC=1.CN(C)C1C=CN=CC=1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([NH:24][C:27]([O:53][CH2:46][C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)=[O:36])([C:17]([F:20])([F:21])[CH:18]=[CH2:19])[CH2:9]1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of an optically-active compound of 3-(1,1-difluoro-allyl)-piperidine-1,3-dicarboxylic acid 1-tert-butyl ester (12.3 g) and triethylamine (11.2 ml) in toluene (123 ml) heated to 100° C. was added dropwise diphenylphosphoryl azide (11.2 ml). The reaction mixture was stirred at 100° C. for 25 minutes, and then thereto were added benzyl alcohol (6.2 ml) and 4-dimethylaminopyridine (0.98 g). The mixture was stirred at 100° C. overnight, and then cooled to room temperature and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1 to 85/15) to give the titled compound (15.1 g).

Workup

stirringThe mixture was stirred at 100° C. overnight
temperaturecooled to room temperature
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=9/1 to 85/15)

Sources & evidence

ORD record: ord-8fbacc24a3a2493b8a41df71755725a5
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08609647B2

Reaction notes

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