Trifluoroacetic acid → N-(2-methylpropyl)-N-[(quinolin-3-yl)methyl]piperidin-4-amine

HRID 2111891Notes

Reaction equation

C(OC([N:8]1[CH2:13][CH2:12][CH:11]([N:14]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:15][C:16]2[CH:17]=[N:18][C:19]3[C:24]([CH:25]=2)=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH2:10][CH2:9]1)=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O>ClCCl>[CH3:28][CH:27]([CH3:29])[CH2:26][N:14]([CH2:15][C:16]1[CH:17]=[N:18][C:19]2[C:24]([CH:25]=1)=[CH:23][CH:22]=[CH:21][CH:20]=2)[CH:11]1[CH2:10][CH2:9][NH:8][CH2:13][CH2:12]1

Participants

Conditions

Temperature: 0 °C

Procedure

4-{Isobutyl-[(quinolin-3-yl)methyl]-amino}-piperidine-1-carboxylic acid tert-butyl ester is added to a stirred solution of dichloromethane (5 ml) and anisole (9.0 ml, 82.8 mmol). The reaction is cooled to 0° C. Trifluoroacetic acid (6.0 ml, 72.9 mmol) is then added. The reaction is stirred for 1 h at 0° C. and then for 2 h at room temperature. The reaction is loaded onto a pre-washed SCX-2 (10 g) column and washed with methanol (200 ml). The product is then eluted with 2M ammonia in methanol (100 ml) and concentrated on a rotary evaporator to yield (0.74 g, 99%) of N-(2-methylpropyl)-N-[(quinolin-3-yl)methyl]piperidin-4-amine: mass spectrum (ion spray): m/z=298.2 (M+1); 1H NMR (CDCl3): δ=8.93 (1H, d), 8.08 (1H, d), 8.02 (1H, d), 7.79-7.77 (1H, m), 7.68-7.64 (1H, m), 7.54-7.50 (1H, m), 3.79 (2H, s), 3.13-3.10 (2H, m), 2.59-2.46 (3H, m), 2.28 (2H, d), 2.06 (1H, br s), 1.80-1.77 (2H, m), 1.72-1.61 (1H, m), 1.55-1.44 (2H, m), 0.84 (6H, d).

Workup

waitfor 2 h at room temperature
washwashed with methanol (200 ml)
washThe product is then eluted with 2M ammonia in methanol (100 ml)
concentrationconcentrated on a rotary evaporator

Sources & evidence

ORD record: ord-6a195dc8fccd4b6484c95e2eefe9e6d9
Source dataset: uspto-grants-2009_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07521462B2

Reaction notes

Loading…