Hydrochloric Acid → 5-chloro-2-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)benzoic acid
Reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].CO.[OH-].[Na+].Cl>>[Cl:1][C:2]1[CH:3]=[C:4]([O:13][CH:14]2[CH2:19][CH2:18][O:17][CH2:16][CH2:15]2)[C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8]Participants
Procedure
Methyl 5-chloro-2-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)benzoate (from the previous step) was dissolved in MeOH (5.04 mL, 125 mmol) and treated with 8M NaOH (1.869 mL, 14.95 mmol). The reaction was stirred at room temperature for 16 h, at which time the solvent was removed in vacuo and the remaining residue diluted with water (6 mL). The mixture was acidified by drop-wise addition of 6 M HCl (2.91 mL, 17.45 mmol) and the resulting suspension was stirred at room temperature for 30 min. The solids were filtered, washed with water (2 mL), and dried under vacuum to give 5-chloro -2-methyl-3-((tetrahydro-2H-pyran-4-yl)oxy)benzoic acid (422 mg, 1.557 mmol, 62.5% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 13.23 (br. s., 1H), 7.33 (d, J=2.02 Hz, 1H), 7.29 (d, J=2.02 Hz, 1H), 4.70 (tt, J=3.85, 8.02 Hz, 1H), 3.76-3.88 (m, 2H), 3.51 (ddd, J=3.03, 8.59, 11.62 Hz, 2H), 2.31 (s, 3H), 1.90-2.03 (m, 2H), 1.53-1.67 (m, 2H). MS(ES) [M+H]+ 271.0.
Workup
- customwas removed in vacuo
- additionthe remaining residue diluted with water (6 mL)
- stirringthe resulting suspension was stirred at room temperature for 30 min
- filtrationThe solids were filtered
- washwashed with water (2 mL)
- customdried under vacuum
Sources & evidence
- ORD record
- ord-6b9ecb686ab14aa79393954b497f4783
- Source dataset
- uspto-grants-2016_07
- Patent number
- US09382234B2
Reaction notes
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