4-(3,3-Difluoro-1,4'-bipiperidin-1'-yl)-2-(methyloxy)aniline → 4-{4-[(3S)-3-fluoro-1-pyrrolidinyl]-1-piperidinyl}-2-(methyloxy)aniline

HRID 1014200Notes

Reaction equation

HRID 1014200 reaction equation
[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([N+:19]([O-])=O)=[C:15]([O:22][CH3:23])[CH:14]=3)[CH2:9][CH2:8]2)[CH2:3]1.FC1(F)CCCN(C2CCN(C3C=CC(N)=C(OC)C=3)CC2)C1>>[F:1][C@H:2]1[CH2:6][CH2:5][N:4]([CH:7]2[CH2:12][CH2:11][N:10]([C:13]3[CH:18]=[CH:17][C:16]([NH2:19])=[C:15]([O:22][CH3:23])[CH:14]=3)[CH2:9][CH2:8]2)[CH2:3]1

Participants

3

Reactant 2

HCID 594416354-(3,3-Difluoro-1,4'-bipiperidin-1'-yl)-2-(methyloxy)aniline2×HCID 594416544-[(3S)-3-fluoro-1-pyrrolidinyl]-1-[3-(methyloxy)-4-nitrophenyl]piperidine

Product 1

HCID 594420514-{4-[(3S)-3-fluoro-1-pyrrolidinyl]-1-piperidinyl}-2-(methyloxy)anilineYield 86.9%

Procedure

4-[(3S)-3-fluoro-1-pyrrolidinyl]-1-[3-(methyloxy)-4-nitrophenyl]piperidine (4 mmol) was reduced in a manner analogous to 4-(3,3-difluoro-1,4′-bipiperidin-1′-yl)-2-(methyloxy)aniline (Intermediate B38). The filtrate was washed with water, dried over MgSO4 and concentrated to give 4-{4-[(3S)-3-fluoro-1-pyrrolidinyl]-1-piperidinyl}-2-(methyloxy)aniline (1.02 g, 86% yield). 1H NMR (400 MHz, d6-DMSO) δ 6.48-6.45 (m, 2H), 6.26 (dd, J=8.4 and 2.4 Hz, 1H), 5.24-5.07 (m, 1H), 4.16 (s, 2H), 3.70 (s, 3H), 3.33-3.30 (m, 2H), 2.88-2.76 (m, 2H), 2.69-2.56 (m,1H), 2.54-2.46 (m under DMSO peak, 2H), 2.37-2.31 (m, 1H), 2.14-1.99 (m, 2H), 1.90-1.75 (m, 3H), 1.51-1.41 (m, 2H).

Workup

  1. washThe filtrate was washed with water
  2. dry with materialdried over MgSO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-0769ce678d4542d38154de09ab96ade7
Source dataset
uspto-grants-2011_07
Patent number
US07981903B2

Reaction notes

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