p-Toluenesulfonic acid monohydrate → Trifluoroacetic acid

HRID 2357101Notes

Reaction equation

HRID 2357101 reaction equation
CC1(C)[N:6](C(OC(C)(C)C)=O)[C@:5]([CH3:39])([C:14]([NH:16][NH:17][C:18](=O)[C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[C:21]([C:34]([F:37])([F:36])[F:35])[CH:20]=2)=O)[CH2:4][O:3]1.[OH2:41].C1(C)C=CC([S:48](O)(=O)=[O:49])=CC=1>CO>[NH2:6][C@@:5]([C:14]1[S:48][C:18]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])=[C:21]([C:34]([F:37])([F:36])[F:35])[CH:20]=2)=[N:17][N:16]=1)([CH3:39])[CH2:4][OH:3].[C:21]([OH:49])([C:34]([F:37])([F:36])[F:35])=[O:41]

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 53349361HCID 53349361, compound

Product 2

HCID 6422Trifluoroacetic acidYield 155.9%HCID 250604211,3,4-Thiadiazole-2-ethanol, beta-amino-beta-methyl-5-[4-(octyloxy)-3-(trifluoromethyl)phenyl]-, (betaS)-

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of (S)-tert-butyl 2,2,4-trimethyl-4-(2-(4-(octyloxy)-3-(trifluoromethyl)-benzoyl)hydrazinecarbonyl)oxazolidine-3-carboxylate (D9) (156 mg, 0.27 mmol) in methanol (10 mL) was treated with p-toluenesulfonic acid monohydrate (259 mg, 1.36 mmol) at 70° C. for 3 hours. Two thirds of the reaction mixture was then purified by prep HPLC on a C8(2) column ((Luna, 5μ, 100×21.10 mm) with acetonitrile-H2O (0.1% TFA) as mobile phase and gradient 30-98% in 20 min. The title compound was obtained as the bis-TFA salt (24 mg). MS (ESI): 432.00 (MH+); 1H NMR (400 MHz, DMSO-d6) δ 8.21 (dd, 1H, J=2.0 Hz, J=8.8 Hz), 8.15 (d, 1H, J=2.0 Hz), 8.09 (br s, 2H), 7.45 (d, 1H, J=8.8 Hz), 5.96 (t, 1H, J=4.8 Hz), 4.21 (t, 2H, J=6.4 Hz), 3.81 (dd, 1H, J=11.2 Hz, J=5.2 Hz), 3.73 (dd, 1H, J=11.2 Hz, J=5.2 Hz), 1.76 (m, 2H), 1.66 (s, 3H), 1.44 (m, 2H), 1.28 (m, 8H), 0.86 (t, 3H, J=6.8 Hz).

Workup

  1. customTwo thirds of the reaction mixture was then purified by prep HPLC on a C8(2) column ((Luna, 5μ, 100×21.10 mm) with acetonitrile-H2O (0.1% TFA) as mobile phase and gradient 30-98% in 20 min

Sources & evidence

ORD record
ord-83680b87b3064c868488233a3398c043
Source dataset
uspto-grants-2010_07
Patent number
US07759370B2

Reaction notes

Loading…