Toluene → HCID 69002715, compound

HRID 2059691Notes

Reaction equation

HRID 2059691 reaction equation
[CH:1]1([C:4]([NH:6][C:7]2[C:15]([OH:16])=[CH:14][C:13]([F:17])=[CH:12][C:8]=2[C:9]([O-:11])=[O:10])=O)[CH2:3][CH2:2]1.O.[C:19]1(C)C=CC(S(O)(=O)=O)=CC=1.C1(C)C=CC=CC=1>C(OCC)(=O)C>[CH:1]1([C:4]2[O:16][C:15]3[C:7](=[C:8]([C:9]([O:11][CH3:19])=[O:10])[CH:12]=[C:13]([F:17])[CH:14]=3)[N:6]=2)[CH2:3][CH2:2]1

Participants

5

Reactant 3

HCID 1140TolueneHCID 521998p-Toluenesulfonic acid monohydrateHCID 178524529HCID 178524529, compound

Product 1

HCID 69002715HCID 69002715, compoundYield 69%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-(cyclopropanecarboxamido)-5-fluoro-3-hydroxybenzoate from Step D (180 mg, 0.71 mmol), p-toluenesulfonic acid monohydrate (202 mg, 1.07 mmol) and toluene (5 mL) was heated at reflux under nitrogen for 3 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate, washed with a saturated solution of sodium bicarbonate and brine, dried over sodium sulfate, filtered and concentrated. The crude material was purified by Combi-flash chromatography (silica gel, 60:40 hexanes/ethyl acetate) to afford methyl 2-cyclopropyl-6-fluorobenzoxazole-4-carboxylate (115 mg, 69%) as a white solid: 1H NMR (300 MHz, CDCl3) δ 7.68 (dd, J=10.2, 2.4 Hz, 1H), 7.34 (dd, J=7.5, 2.4 Hz, 1H), 4.02 (s, 3H), 2.39-2.29 (m, 1H), 1.35-1.29 (m, 2H), 1.26-1.17 (m, 2H); 19F NMR (282 MHz, CDCl3) δ 116.29; MS (ESI+) m/z 236 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux under nitrogen for 3 h
  3. washwashed with a saturated solution of sodium bicarbonate and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude material was purified by Combi-flash chromatography (silica gel, 60:40 hexanes/ethyl acetate)

Sources & evidence

ORD record
ord-ad1bce2eab464da6b2e85b66de173753
Source dataset
uspto-grants-2012_10
Patent number
US08278301B2

Reaction notes

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