Potassium Carbonate → 2-(4-Hydroxy-2-methyl-phenyl)-4-isopropyl-thiazole-5-carboxylic acid ethyl ester

HRID 250237

Reaction equation

[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9](Br)=[N:8][C:7]=1[CH:12]([CH3:14])[CH3:13])=[O:5])[CH3:2].[CH3:15][C:16]1[CH:17]=[C:18]([OH:31])[CH:19]=[CH:20][C:21]=1B1OC(C)(C)C(C)(C)O1.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.O>[CH2:1]([O:3][C:4]([C:6]1[S:10][C:9]([C:21]2[CH:20]=[CH:19][C:18]([OH:31])=[CH:17][C:16]=2[CH3:15])=[N:8][C:7]=1[CH:12]([CH3:14])[CH3:13])=[O:5])[CH3:2]

Participants

Conditions

Temperature: 100 °C

Procedure

To a solution of 2-bromo-4-isopropyl-thiazole-5-carboxylic acid ethyl ester (834 mg, 3 mmol), 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (1.4 g, 6 mmol) and K2CO3 (828 mg, 6 mmol) in 1,4-dioxane/H2O (30 mL/5 mL) is bubbled nitrogen gas for 10 minutes. To this solution is added tetrakistriphenylphosphine palladium (173 mg, 0.15 mmol). The reaction mixture is stirred at 100° C. overnight. The reaction mixture is concentrated under reduced pressure and the residue is partitioned between EtOAc and 1N HCl. The organic phase is concentrated and purified by column chromatography (gradient: 0 to 15% EtOAc in hexanes) to give the title product (730 mg, 80%). 1H NMR (DMSO-d6) δ 9.99 (s, 1H), 7.68 (d, 1H), 6.68, 6.72 (m, 2H), 4.26 (q, 2H), 3.88 (m, 1H), 2.50 (s, 3H), 1.26 (t, 3H), 1.23 (d, 6H).

Workup

concentrationThe reaction mixture is concentrated under reduced pressure
customthe residue is partitioned between EtOAc and 1N HCl
concentrationThe organic phase is concentrated
custompurified by column chromatography (gradient: 0 to 15% EtOAc in hexanes)

Sources & evidence

ORD record: ord-1e497956815d4af6baa589ccc1cc8d2d
Source dataset: uspto-grants-2011_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07863302B2

Linked notes

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