p-Toluenesulfonic acid monohydrate → 2-(4-isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide

HRID 254715

Reaction equation

O[C:2]([C:5]1[CH:10]=[CH:9][C:8]([CH2:11][C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:27])[F:26])=[CH:19][N:18]=2)[CH3:16])=[O:13])=[CH:7][CH:6]=1)([CH3:4])[CH3:3].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.C(Cl)Cl>[C:2]([C:5]1[CH:6]=[CH:7][C:8]([CH2:11][C:12]([NH:14][C@@H:15]([C:17]2[CH:22]=[CH:21][C:20]([O:23][CH2:24][C:25]([F:28])([F:26])[F:27])=[CH:19][N:18]=2)[CH3:16])=[O:13])=[CH:9][CH:10]=1)([CH3:4])=[CH2:3]

Participants

Conditions

Temperature: 100 °C

Procedure

A mixture of 2-[4-(1-hydroxy-1-methylethyl)phenyl]-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide (400 mg, 1.01 mmol) and p-toluenesulfonic acid monohydrate (38.4 mg, 0.202 mmol) in toluene (4.5 mL) was heated at 100° C. in a sealed tube for 6 h. The mixture was cooled to room temperature, diluted with CH2Cl2 (40 mL) and washed with water (2×50 mL). The organic layer was dried over MgSO4, concentrated and purified by normal phase chromatography (20-100% EtOAc/Hexanes) to give 316 mg (83%) of 2-(4-isopropenylphenyl)-N-{(1R)-1-[5-(2,2,2-trifluoroethoxy)pyridin-2-yl]ethyl}acetamide as a white solid. 1H NMR (CDCl3, 400 MHz) δ 8.21 (d, J=2.35 Hz, 1H), 7.45 (m, 2H), 7.20 (m, 4H), 6.64 (d, J=7.32 Hz, 1H), 5.38 (s, 1H), 5.11 (m, 1H), 5.09 (s, 1H), 4.37 (q, J=7.94 Hz, 2H), 3.58 (s, 2H), 2.15 (s, 3H), 1-39 (d, J=6.77 Hz, 3H); MS (Electrospray): m/z 379.5 (M+H).

Workup

temperatureThe mixture was cooled to room temperature
washwashed with water (2×50 mL)
dry with materialThe organic layer was dried over MgSO4
concentrationconcentrated
custompurified by normal phase chromatography (20-100% EtOAc/Hexanes)

Sources & evidence

ORD record: ord-01811a6dadc44a968f98dad21a642a37
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07875636B2

Linked notes

Loading…