p-Toluenesulfonic acid monohydrate → HCID 10183477, compound

HRID 478913Notes

Reaction equation

HRID 478913 reaction equation
[F:1][C:2]1[CH:33]=[CH:32][C:5]([CH2:6][CH:7]2[CH2:12][CH2:11][N:10]([CH2:13][C:14]3([C:29]([OH:31])=[O:30])[O:18][N:17]=[C:16]([C:19]4[CH:28]=[CH:27][C:22]5[NH:23][C:24](=[O:26])[O:25][C:21]=5[CH:20]=4)[CH2:15]3)[CH2:9][CH2:8]2)=[CH:4][CH:3]=1.O.[C:35]1(C)C=CC(S(O)(=O)=O)=CC=1>CO.C(O)(C(F)(F)F)=O>[CH3:35][O:30][C:29]([C:14]1([CH2:13][N:10]2[CH2:9][CH2:8][CH:7]([CH2:6][C:5]3[CH:32]=[CH:33][C:2]([F:1])=[CH:3][CH:4]=3)[CH2:12][CH2:11]2)[O:18][N:17]=[C:16]([C:19]2[CH:28]=[CH:27][C:22]3[NH:23][C:24](=[O:26])[O:25][C:21]=3[CH:20]=2)[CH2:15]1)=[O:31]

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 10204430HCID 10204430, compound

Product 1

HCID 10183477HCID 10183477, compoundYield 31.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6422Trifluoroacetic acidSolvent

Procedure

To a solution of 5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazole-5-carboxylic acid (687 mg, 0.909 mmol) in MeOH (20 mL) and TFA (1.5 mL) was added p-toluenesulfonic acid monohydrate (190 mg, 0.999 mmol). The reaction mixture was heated to reflux overnight, then concentrated and purified by flash chromatography (silica gel, 5% MeOH in CH2Cl2) to give 5-[4-(4-fluorobenzyl)piperidin-1-ylmethyl]-3-(2-oxo-2,3-dihydrobenzoxazol-6-yl)-4,5-dihydroisoxazole-5-carboxylic acid methyl ester (133 mg, 31%), as an off white solid:

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureto reflux overnight
  3. concentrationconcentrated
  4. custompurified by flash chromatography (silica gel, 5% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-a33b8d7ba74c48e39a3bf3390e13a242
Source dataset
uspto-grants-2003_11
Patent number
US06642256B2

Reaction notes

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