(3R)-3-fluoropyrrolidine hydrochloride → (R)-4-(3-Fluoropyrrolidin-1-yl)-1-(3-methoxy-4-nitrophenyl)piperidine

HRID 1014197Notes

Reaction equation

HRID 1014197 reaction equation
COC1C=C(N2CCC(=O)CC2)C=CC=1[N+]([O-])=O.Cl.F[C@@H]1CCNC1.[F:26][C:27]1(F)[CH2:32]C[CH2:30][N:29]([CH:33]2[CH2:38][CH2:37][N:36]([C:39]3[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[C:41]([O:48][CH3:49])[CH:40]=3)[CH2:35][CH2:34]2)[CH2:28]1>>[F:26][C@@H:27]1[CH2:32][CH2:30][N:29]([CH:33]2[CH2:38][CH2:37][N:36]([C:39]3[CH:44]=[CH:43][C:42]([N+:45]([O-:47])=[O:46])=[C:41]([O:48][CH3:49])[CH:40]=3)[CH2:35][CH2:34]2)[CH2:28]1

Participants

4

Reactant 3

HCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 259188571-(3-Methoxy-4-nitrophenyl)piperidin-4-oneHCID 594418643,3-Difluoro-1'-[3-(methyloxy)-4-nitrophenyl]-1,4'-bipiperidine

Product 1

HCID 58071437(R)-4-(3-Fluoropyrrolidin-1-yl)-1-(3-methoxy-4-nitrophenyl)piperidineYield 100%

Procedure

1-[3-(methyloxy)-4-nitrophenyl]-4-piperidinone (1.0 g, 4.0 mmol) and commercially available (R)-(−)-3-fluoropyrrolidine hydrochloride were subjected to a reductive amination analogous to the procedure for 3,3-difluoro-1′-[3-(methyloxy)-4-nitrophenyl]-1,4′-bipiperidine (Intermediate B41) to give 4-[(3R)-3-fluoro-1-pyrrolidinyl]-1-[3-(methyloxy)-4-nitrophenyl]piperidine (1.3 g, 100% yield). 1H NMR (400 MHz, d6-DMSO) δ 7.84 (d, J=9.6 Hz, 1H), 6.56 (dd, J=9.6 and 2.0 Hz, 1H), 6.47 (d, J=2.0 Hz, 1H), 5.24-5.07 (m, 1H), 3.91-3.87 (m, 5H), 3.05-2.99 (m, 2H), 2.88-2.77 (m, 2H), 2.70-2.58 (m, 1H), 2.38-2.27 (m, 2H), 2.13-2.00 (m,1H), 1.88-1.75 (m, 3H), 1.46-1.36 (m, 2H).

Sources & evidence

ORD record
ord-492b6273d5594ca2b692e19d5bc6beba
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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