tert-Butanol → (2-Methyl-4-o-tolyl-thiazol-5-yl)-carbamic acid tert-butyl ester

HRID 474353Notes

Reaction equation

[CH3:1][C:2]1[S:3][C:4](C(O)=O)=[C:5]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=2[CH3:13])[N:6]=1.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:24])C=CC=CC=1.C([N:36]([CH2:39]C)CC)C.[C:41]([OH:45])([CH3:44])([CH3:43])[CH3:42]>O>[C:41]([O:45][C:39](=[O:24])[NH:36][C:4]1[S:3][C:2]([CH3:1])=[N:6][C:5]=1[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][C:8]=1[CH3:13])([CH3:44])([CH3:43])[CH3:42]

Participants

Conditions

Temperature: 85 °C

Procedure

A mixture of 2-methyl-4-o-tolyl-thiazole-5-carboxylic acid (300 mg, 1.29 mmol, 1.0 equiv), diphenyl phosphorylazide (DPPA) (354 mg, 1.29 mmol, 1.0 equiv), and triethylamine (130 mg, 1.29 mmol, 1.0 equiv) in tert-butanol (10 mL) was heated to 85° C. for 4 hours. After cooling, the mixture was diluted with water and extracted with ethyl acetate (3×). The combined organic extracts were dried over magnesium sulphate, filtered, and concentrated under vacuum. The residue was purified by flash column chromatography on silica gel (gradient: 2 to 25% ethyl acetate in pentane) to give 352 mg (90%) of (2-methyl-4-o-tolyl-thiazol-5-yl)-carbamic acid tert-butyl ester as an oil. LCMS (ESI) m+H=305.1; 1H NMR (400 MHz, CDCl3) δ: 7.33-7.24 (m, 4H), 6.58 (s, 1H), 2.64 (s, 3H), 2.24 (s, 3H), 1.48 (s, 9H).

Workup

temperatureAfter cooling
extractionextracted with ethyl acetate (3×)
dry with materialThe combined organic extracts were dried over magnesium sulphate
filtrationfiltered
concentrationconcentrated under vacuum
customThe residue was purified by flash column chromatography on silica gel (gradient: 2 to 25% ethyl acetate in pentane)

Sources & evidence

ORD record: ord-2897ac48fb074552a47e96389d40c5f3
Source dataset: uspto-grants-2014_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08637526B2

Reaction notes

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