Hydrochloric Acid → 2-Chloro-4-morpholinobenzoic acid
Reaction equation
C[O:2][C:3](=[O:17])[C:4]1[CH:9]=[CH:8][C:7]([N:10]2[CH2:15][CH2:14][O:13][CH2:12][CH2:11]2)=[CH:6][C:5]=1[Cl:16].[OH-].[Na+].Cl>CO.O>[Cl:16][C:5]1[CH:6]=[C:7]([N:10]2[CH2:11][CH2:12][O:13][CH2:14][CH2:15]2)[CH:8]=[CH:9][C:4]=1[C:3]([OH:17])=[O:2]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 2
Procedure
A mixture of 2-chloro-4-morpholin-4-yl-benzoic acid methyl ester (3.08 g, 12.0 mmol) and 6N NaOH (2.5 mL, 15 mmol) in methanol (50 mL) and water (7.5 mL) was stirred 24 h at room temperature, then acidified with 2N HCl. The precipitate was filtered off, washed with water and dried to provide 2-chloro-4-morpholin-4-yl-benzoic acid (2.56 g, 88% yield) as a white solid. This intermediate (10.6 mmol) was suspended in tert-butanol (20 mL), treated with diphenylphosphoryl azide (2.30 mL, 10.6 mmol), then with triethylamine (1.45 mL, 10.6 mmol), was stirred at reflux for 20 h and evaporated. Purification by flash chromatography (SiO2) eluted with 2:8 ethyl acetate:hexanes provided (2-chloro-4-morpholin-4-yl-phenyl)-carbamic acid tert-butyl ester (2.84 g) as a mixture (˜1:1) with 2-chloro-4-morpholin-4-yl-benzoic acid tert-butyl ester. This mixture was carried on without further purification. 1H-NMR (CDCl3, 500 MHz) 8.0 (br, 1H), 7.80 (d, 1H), 7.4 (d, 1H), 6.90 (d, 1H), 6.87 (d, 1H), 6.84 (dd, 1H), 6.75 (dd, 1H), 3.87 (m, 8H), 3.26 (m, 4H), 3.11 (m, 4H), 1.61 (s, 9H), 1.55 (s, 9H) ppm; MS (FIA) 313.1 (M+H); HPLC (Method A) 3.70 min.
Workup
- filtrationThe precipitate was filtered off
- washwashed with water
- customdried
Sources & evidence
- ORD record
- ord-97b5701a97a746e19ef576e603639c88
- Source dataset
- uspto-grants-2011_03
- Patent number
- US07902239B2
Reaction notes
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