4-Hydroxybenzoic Acid → 3,5-Difluorobenzamide mono-4-hydroxybenzoate

HRID 445145Notes

Reaction equation

HRID 445145 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:5]([NH2:7])=[O:6].[OH:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=1>C(OC(C)C)(=O)C.C1COCC1>[OH:12][C:13]1[CH:21]=[CH:20][C:16]([C:17]([OH:19])=[O:18])=[CH:15][CH:14]=1.[F:1][C:2]1[CH:3]=[C:4]([CH:8]=[C:9]([F:11])[CH:10]=1)[C:5]([NH2:7])=[O:6]

Participants

5

Reactant 2

HCID 1354-Hydroxybenzoic AcidHCID 27369103,5-Difluorobenzamide

Product 1

HCID 866585813,5-Difluorobenzamide mono-4-hydroxybenzoate

Reagents, catalysts & solvents 2

HCID 7915Isopropyl AcetateSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 71.5 mg (0.20 mmol) of (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide in 3.5 mL of isopropyl acetate was added 100 μL (0.1 mmol, 0.5 eq) of a 1M 4-hydroxylbenzoic acid in THF solution. The isopropyl acetate was evaporated to yield (2S,3R)-N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide mono-4-hydroxybenzoate as a solid which was collected and dried under vacuum at 25° C. for 24 h. mp(DSC)=106.0° C. 1H NMR (400 MHz, DMSO-d6) δ 10.23 (br s), 8.43 (s, 1H), 8.29 (s, 1H), 8.28 (s, 1H), 7.78 (d, 1H), 7.61 (m, 1H), 7.41 (m, 3H), 7.22 (m, 1H), 6.80 (d, 1H), 3.66 (m, 1H), 2.70-3.20 (m, 7H), 1.50-1.90 (m, 4H), 1.20 (m, 1H).

Workup

  1. customThe isopropyl acetate was evaporated

Sources & evidence

ORD record
ord-974b24f75a054014a2959882fa5b9e99
Source dataset
uspto-grants-2013_07
Patent number
US08476296B2

Reaction notes

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