Sodium Hydroxide → 2'-(Difluoromethyl)-2-methylbiphenyl-4-carboxylic acid

HRID 572540Notes

Reaction equation

[OH-].[Na+].[F:3][CH:4]([F:22])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([O:19]C)=[O:18])=[CH:13][C:12]=1[CH3:21]>CCO>[F:3][CH:4]([F:22])[C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[C:11]1[CH:16]=[CH:15][C:14]([C:17]([OH:19])=[O:18])=[CH:13][C:12]=1[CH3:21]

Participants

Conditions

Temperature: 70 °C

Procedure

A 5 N aqueous solution of NaOH (1.5 mL, 7.5 mmol) was added into a solution of methyl 2′-(difluoromethyl)-2-methylbiphenyl-4-carboxylate (1.4 g, 5.1 mmol) in EtOH (15 mL). The resulting mixture was heated at 70° C. for 1 hour, and then evaporated. The residue was taken up with water (25 mL) and a 5N aqueous solution of HCl (3 mL), and then extracted with MTBE (2×50 mL). The organic layers were washed with brine (25 mL), combined, dried (MgSO4) and concentrated reduced pressure to give the title compound as a white powder (1.3 g, 93%). HPLC (Method A) Rt 4.2 min (purity: 98.9%). LC/MS (Method B): 261.1 (M−H)−. 1H NMR (DMSO-d6, 300 MHz) δ 13.1 (s, 1H), 7.90 (s, 1H), 7.82 (dd, J=7.9, 1.4 Hz, 1H), 7.74 (m, 1H), 7.66-7.55 (m, 2H), 7.26 (m, 2H), 6.55 (t, J=55 Hz, 1H), 2.05 (s, 3H).

Workup

customevaporated
extractiona 5N aqueous solution of HCl (3 mL), and then extracted with MTBE (2×50 mL)
washThe organic layers were washed with brine (25 mL)
dry with materialdried (MgSO4)
concentrationconcentrated reduced pressure

Sources & evidence

ORD record: ord-177c1f30524f42c3abadc50eda9c1fbc
Source dataset: uspto-grants-2015_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09029405B2

Reaction notes

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