Lithium hydroxide, monohydrate → 2-(2-Phenylpyrimidin-5-yl)thiazole-4-carboxylic acid

HRID 2096348

Reaction equation

HRID 2096348 reaction equation
O.[OH-].[Li+].[C:4]1([C:10]2[N:15]=[CH:14][C:13]([C:16]3[S:17][CH:18]=[C:19]([C:21]([O:23]C(C)(C)C)=[O:22])[N:20]=3)=[CH:12][N:11]=2)[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>C(O)C.O.CN(C=O)C>[C:4]1([C:10]2[N:15]=[CH:14][C:13]([C:16]3[S:17][CH:18]=[C:19]([C:21]([OH:23])=[O:22])[N:20]=3)=[CH:12][N:11]=2)[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 59252449Tert-butyl 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylate

Product 1

HCID 592524752-(2-Phenylpyrimidin-5-yl)thiazole-4-carboxylic acidYield 87%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution consisting of lithium hydroxide monohydrate (0.38 g, 9.0 mmol) dissolved in ethanol (20 mL)/water (10 mL) was added tert-butyl 2-(2-phenylpyrimidin-5-yl)thiazole-4-carboxylate (Example 62, 705 mg, 3.0 mmol) in dry DMF (11 mL) and the mixture stirred at room temperature for 18 hours. Ethanol was removed under reduced pressure and the solution diluted with water and subsequently extracted with diethyl ether (2×30 mL). The aqueous phase was acidified with 2 N hydrochloric acid to pH2. The solid precipitate was filtered, washed with water and dried under high vacuum to give the title compound as an off-white solid (371 mg, 87% yield); Rf 0.15 with 9:1 v/v dichloromethane-methanol; 1H-NMR (300 MHz; DMSO-d6) δ 9.39 (s, 2H), 8.63 (s, 1H), 8.44 (dd, 2H), 7.55 (m, 3H); MS (ESI+) m/z 284 (M+1); H-PGDS FPBA IC50: 1.1 μM.

Workup

  1. customEthanol was removed under reduced pressure
  2. additionthe solution diluted with water
  3. extractionsubsequently extracted with diethyl ether (2×30 mL)
  4. filtrationThe solid precipitate was filtered
  5. washwashed with water
  6. customdried under high vacuum

Sources & evidence

ORD record
ord-0f936a57ad42468192f84c586a399405
Source dataset
uspto-grants-2013_05
Patent number
US08450326B2

Linked notes

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