4-Nitrobenzoic Acid → Benzyl trans-3-fluoro-4-[(4-nitrobenzyl)oxy]piperidine-1-carboxylate

HRID 1926648Notes

Reaction equation

C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[F:34][C@H:35]1[C@@H:40]([OH:41])[CH2:39][CH2:38][N:37]([C:42]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:43])[CH2:36]1.[N+:52]([C:55]1[CH:63]=[CH:62][C:58]([C:59](O)=O)=[CH:57][CH:56]=1)([O-:54])=[O:53]>C1COCC1>[F:34][C@H:35]1[C@H:40]([O:41][CH2:59][C:58]2[CH:62]=[CH:63][C:55]([N+:52]([O-:54])=[O:53])=[CH:56][CH:57]=2)[CH2:39][CH2:38][N:37]([C:42]([O:44][CH2:45][C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=2)=[O:43])[CH2:36]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of triphenylphosphine (120.1 g, 0.458 mol) in THF (2 L) was added DIAD (92.6 g, 0.458 mol) with stirring under nitrogen at 0° C. The resulting suspension was stirred for 40 min, and then a solution of benzyl cis-3-fluoro-4-hydroxypiperidine-1-carboxylate (58 g, 0.229 mol) and 4-nitrobenzoic acid (45.9 g, 0.275 mol) in THF was added slowly over 1.5 h. The resulting orange solution was allowed to warm to room temperature and stirred for 48 h. The mixture was concentrated under reduced pressure to a crude oil was purified by column chromatography (EtOAc:petroleum ether=1:40) to afford benzyl trans-3-fluoro-4-[(4-nitrobenzyl)oxy]piperidine-1-carboxylate as an off-white solid.

Workup

stirringThe resulting suspension was stirred for 40 min
temperatureto warm to room temperature
stirringstirred for 48 h
concentrationThe mixture was concentrated under reduced pressure to a crude oil
customwas purified by column chromatography (EtOAc:petroleum ether=1:40)

Sources & evidence

ORD record: ord-0f417f513be748a59111fec991e35afa
Source dataset: uspto-grants-2012_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08183245B2

Reaction notes

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