Trimethyl orthoacetate → Benzoic acid, 4-[2-[4-(2-methoxyethyl)-1-piperazinyl]-4-thiazolyl]-

HRID 606570Notes

Reaction equation

[CH3:1][O:2][C:3](OC)(OC)[CH3:4].[N:9]1([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:28]=[CH:27][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=3)[N:19]=2)[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C([BH3-])#N.[Na+]>Cl.C(#N)C.C([O-])(=O)C.[Na+]>[CH3:1][O:2][CH2:3][CH2:4][N:12]1[CH2:13][CH2:14][N:9]([C:15]2[S:16][CH:17]=[C:18]([C:20]3[CH:21]=[CH:22][C:23]([C:24]([OH:26])=[O:25])=[CH:27][CH:28]=3)[N:19]=2)[CH2:10][CH2:11]1

Participants

Conditions

Temperature: 50 °C

Procedure

4-[4-(4-Carboxy-phenyl)-thiazol-2-yl]-piperazine-1-carboxylic acid tert-butyl ester (5.0 mmol) was dissolved in hydrochloric acid in dioxane (4N, 25 ml) and the reaction stirred at RT for 2 h. The reaction was concentrated in vacuo to yield 4-(2-piperazin-1-yl-thiazol-4-yl)-benzoic acid. Trimethoxyethane (6.5 mmol) was dissolved in aqueous hydrochloric acid (1N, 10 ml) and the reaction heated at 50° C. for 1.5 h. The reaction was allowed to cool to RT and was then added to a suspension of 4-(2-piperazin-1-yl-thiazol-4-yl)-benzoic acid (5.0 mmol) in acetonitrile (25 ml) and sodium acetate buffer (1N, pH 5.5, 10 ml). The reaction was stirred at RT for 1.5 h. Sodium cyanoborohydride (6.5 mol) was added and the reaction stirred at RT for 16 h. The reaction was concentrated in vacuo and the product purified by flash chromatography (silica gel, 10% methanol in dichloromethane) to give the title product as a colourless oil (0.9 g). m/z=348 (100% M+H) in MS ES+.

Workup

temperatureto cool to RT
stirringthe reaction stirred at RT for 16 h
concentrationThe reaction was concentrated in vacuo
customthe product purified by flash chromatography (silica gel, 10% methanol in dichloromethane)

Sources & evidence

ORD record: ord-185e9e6e50c5478fb233f0c9c0c1b0dc
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915300B2

Reaction notes

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