Water → HCID 23075278, compound

HRID 2076438Notes

Reaction equation

HRID 2076438 reaction equation
[F:1][C:2]([F:30])([C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([CH3:27])([CH3:26])[CH2:21][CH2:20][C:19]2([CH3:29])[CH3:28])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][CH:15]=1)[C:9]([O:11]C)=[O:10])=[O:4].O.[OH-].[K+]>CO>[F:1][C:2]([F:30])([C:16]1[CH:17]=[C:18]2[C:23](=[CH:24][CH:25]=1)[C:22]([CH3:26])([CH3:27])[CH2:21][CH2:20][C:19]2([CH3:29])[CH3:28])[C:3]([NH:5][C:6]1[CH:7]=[C:8]([CH:13]=[CH:14][CH:15]=1)[C:9]([OH:11])=[O:10])=[O:4]

Participants

5

Reactant 3

HCID 962WaterHCID 14797Potassium HydroxideHCID 23075289HCID 23075289, compound

Product 1

HCID 23075278HCID 23075278, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
70 °C

Procedure

Methyl 3-(2,2-difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)benzoate 19 (0.50 g, 1.20 mmol) was dissolved in methanol (33.5 mL). Water (3.35 mL) was added via syringe at RT and KOH (0.27 g, 4.81 mmol) was added. The reaction mixture was heated at 70° C. for 2 h. After cooling to RT the mixture was evaporated in vacuo. The crude product was dissolved in water (30 mL) and extracted with ether (2×50 mL). The aqueous layer was acidified by a solution of HCl 1M to about pH=1. The aqueous layer was extracted with ether (2×100 mL), dried over MgSO4, filtered and evaporated. The crude product was purified by column chromatography using as eluent cyclohexane: EtOAc=98:02. 3-(2,2-Difluoro-2-(1,2,3,4-tetrahydro-1,1,4,4-tetramethylnaphthalen-6-yl)acetamido)benzoic acid 20 was obtained (0.41 g, 84% yield) as an orange solid.

Workup

  1. temperatureAfter cooling to RT the mixture
  2. customwas evaporated in vacuo
  3. dissolutionThe crude product was dissolved in water (30 mL)
  4. extractionextracted with ether (2×50 mL)
  5. extractionThe aqueous layer was extracted with ether (2×100 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. customThe crude product was purified by column chromatography

Sources & evidence

ORD record
ord-e283aa08e1084e858a97158ac27c037a
Source dataset
uspto-grants-2011_04
Patent number
US07923579B2

Reaction notes

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