Ethyl orthoformate → HCID 59375009, compound

HRID 1811014Notes

Reaction equation

HRID 1811014 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([OH:6])=O.[Br:12][C:13]1[C:14]([CH3:20])=[C:15]([CH:17]=[CH:18][CH:19]=1)[NH2:16].[CH2:21](OC(OCC)OCC)C>C1COCC1.CCOC(C)=O>[Br:12][C:13]1[C:14]([CH3:20])=[C:15]([N:16]2[C:4](=[O:6])[C:3]3[C:2](=[CH:10][CH:9]=[C:8]([F:11])[CH:7]=3)[N:1]=[CH:21]2)[CH:17]=[CH:18][CH:19]=1

Participants

6

Reactant 3

HCID 31214Ethyl orthoformateHCID 1014122-Amino-5-fluorobenzoic acidHCID 1235383-Bromo-o-toluidine

Product 1

HCID 59375009HCID 59375009, compoundYield 56%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

A mixture of 2-amino-5-fluorobenzoic acid (1.00 g, 6.45 mmol), 3-bromo-2-methylaniline (1.199 g, 6.45 mmol) and triethoxymethane (0.955 g, 6.45 mmol) in THF (2 mL) was heated at 110° C. overnight in a sealed tube. The mixture was cooled to rt and diluted with EtOAc. The solution was washed with NaHCO3 (aq) and water, then was dried and concentrated. The residue was purified by column chromatography (eluting with a gradient from 80:20 to 70:30 hexane-EtOAc) to give 3-(3-bromo-2-methylphenyl)-6-fluoroquinazolin-4(3H)-one as a white solid (1.2 g, 56%). 1H NMR (400 MHz, chloroform-d) δ 8.00 (1 H, dd, J=8.4, 3.1 Hz), 7.93 (1 H, s), 7.81 (1 H, dd, J=9.0, 4.8 Hz), 7.74 (1 H, dd, J=6.9, 2.3 Hz), 7.50-7.58 (1 H, m), 7.21-7.26 (2 H, m), 2.25 (3 H, s). Mass spectrum m/z 333, 335 (M+H)+.

Workup

  1. temperatureThe mixture was cooled to rt
  2. washThe solution was washed with NaHCO3 (aq) and water
  3. customwas dried
  4. concentrationconcentrated
  5. customThe residue was purified by column chromatography (
  6. washeluting with a gradient from 80:20 to 70:30 hexane-EtOAc)

Sources & evidence

ORD record
ord-3db66e69c8e4438d86b21cb921d5fdda
Source dataset
uspto-grants-2013_01
Patent number
US08362065B2

Reaction notes

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