p-Toluenesulfonic acid monohydrate → 2-Amino-5-(1-propoxy-propyl)-4-trifluoromethyl-benzoic acid methyl ester

HRID 906520Notes

Reaction equation

HRID 906520 reaction equation
[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([CH:10]([OH:13])[CH2:11][CH3:12])[C:7]([C:14]([F:17])([F:16])[F:15])=[CH:6][C:5]=1[NH:18]C(=O)C.O.[C:24]1(C)[CH:29]=CC(S(O)(=O)=O)=C[CH:25]=1>C(O)CC.O.CCOC(C)=O>[CH3:1][O:2][C:3](=[O:22])[C:4]1[CH:9]=[C:8]([CH:10]([O:13][CH2:25][CH2:24][CH3:29])[CH2:11][CH3:12])[C:7]([C:14]([F:15])([F:16])[F:17])=[CH:6][C:5]=1[NH2:18]

Participants

6

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 591644582-Acetylamino-5-(1-hydroxy-propyl)-4-trifluoromethyl-benzoic acid methyl ester

Product 1

HCID 119653802-Amino-5-(1-propoxy-propyl)-4-trifluoromethyl-benzoic acid methyl esterYield 139.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 10311-PropanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 2-acetylamino-5-(1-hydroxy-propyl)-4-trifluoromethyl-benzoic acid methyl ester (200 mg, 0.626 mmol) in 1-propanol (2 mL) at r.t. was treated with p-toluenesulfonic acid monohydrate (38 mg, 0.198 mmol) and the reaction was stirred for 10 d at r.t. The reaction mixture was diluted with water and EtOAc and basified to pH 8 with sat. aq KHCO3. The organic phase was washed with brine, dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash chromatography (20 g silica gel, EtOAc/hexanes (0:1→3:7)) to give the title product (88 mg, 44% yield) as light yellow oil. ESI-MS: m/z 320 [M+H]+, m/z 318 [M−H]−.

Workup

  1. washThe organic phase was washed with brine
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash chromatography (20 g silica gel, EtOAc/hexanes (0:1→3:7))

Sources & evidence

ORD record
ord-ad56a52a56704834acb84a16e7cd3b94
Source dataset
uspto-grants-2011_09
Patent number
US08012988B2

Reaction notes

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