Trimethyl orthoformate → 1-Benzooxazol-5-yl-cyclopropanecarboxylic acid methyl ester

HRID 640590Notes

Reaction equation

HRID 640590 reaction equation
[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]([OH:14])=[C:10]([NH2:15])[CH:9]=2)[CH2:7][CH2:6]1)=[O:4].[CH:16](OC)(OC)OC.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CN(C=O)C.O>[CH3:1][O:2][C:3]([C:5]1([C:8]2[CH:13]=[CH:12][C:11]3[O:14][CH:16]=[N:15][C:10]=3[CH:9]=2)[CH2:7][CH2:6]1)=[O:4]

Participants

6

Reactant 3

HCID 9005Trimethyl orthoformateHCID 521998p-Toluenesulfonic acid monohydrateHCID 591293241-(3-Amino-4-hydroxy-phenyl)-cyclopropanecarboxylic acid methyl ester

Product 1

HCID 591292661-Benzooxazol-5-yl-cyclopropanecarboxylic acid methyl esterYield 98.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 1-(3-amino-4-hydroxy-phenyl)-cyclopropanecarboxylic acid methyl ester (3.00 g, 14.5 mmol) in DMF were added trimethyl orthoformate (5.30 g, 14.5 mmol) and a catalytic amount of p-toluenesulfonic acid monohydrate (0.3 g) at room temperature. The mixture was stirred for 3 hours at room temperature. The mixture was diluted with water and extracted with EtOAc (100 mL×3). The combined organic layers were dried over anhydrous Na2SO4 and evaporated under vacuum to give crude 1-benzooxazol-5-yl-cyclopropanecarboxylic acid methyl ester (3.1 g), which was directly used in the next step. 1H NMR (CDCl3, 400 MHz) δ 8.09 (s, 1), 7.75 (d, J=1.2 Hz, 1H), 7.53-7.51 (m, 1H), 7.42-7.40 (m, 1H), 3.66 (s, 3H), 1.69-1.67 (m, 2H), 1.27-1.24 (m, 2H).

Workup

  1. customat room temperature
  2. extractionextracted with EtOAc (100 mL×3)
  3. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  4. customevaporated under vacuum

Sources & evidence

ORD record
ord-4b87ef2d835c44deab509f73d7aa7ccc
Source dataset
uspto-grants-2010_04
Patent number
US07691902B2

Reaction notes

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