Lithium Hydroxide → 2-{[(4-{2-[(2,4-Difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}benzoic acid

HRID 899870Notes

Reaction equation

HRID 899870 reaction equation
[F:1][C:2]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:6](=[O:26])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([S:14][CH2:15][C:16]2[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=2[C:18]([O:20]C)=[O:19])=[CH:10][CH:9]=1.[OH-].[Li+]>C1COCC1.O>[F:1][C:2]1[CH:37]=[C:36]([F:38])[CH:35]=[CH:34][C:3]=1[CH2:4][N:5]([CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33])[C:6](=[O:26])[CH2:7][C:8]1[CH:9]=[CH:10][C:11]([S:14][CH2:15][C:16]2[CH:25]=[CH:24][CH:23]=[CH:22][C:17]=2[C:18]([OH:20])=[O:19])=[CH:12][CH:13]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 69120607Methyl 2-{[(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}benzoate

Product 1

HCID 104595092-{[(4-{2-[(2,4-Difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}benzoic acidYield 56.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-{[(4-{2-[(2,4-difluorobenzyl)(heptyl)amino]-2-oxoethyl}phenyl)thio]methyl}-benzoate (31 mg, 0.057 mmol) was dissolved in THF (1 ml) and cooled in an ice-bath. Lithium hydroxide (2 mg, 0.075 mmol) in water (1 ml) was added. After the addition, the cooling bath was removed and the mixture was stirred overnight. LC-MS showed there was very little product. More lithium hydroxide (3 mg) was added and the mixture was stirred for 6 days more and HPLC showed about 30% product. More (3 mg) of lithium hydroxide was added and the mixture was stirred for 13 days more. It was evaporated in vacuum to remove THF. The residue was acidified with 10% hydrochloric acid, pH˜3, and extracted with ethyl acetate (×2). The organic phases were combined, dried (magnesium sulphate) and evaporated. Chromatography of the residue on a column (ISOLUTE® SI, 500 g/3 ml) using DCM, MeOH/DCM (0.5:99.5) as eluant gave 17 mg desired product, yield 56%.

Workup

  1. temperaturecooled in an ice-bath
  2. additionAfter the addition
  3. customthe cooling bath was removed
  4. additionMore lithium hydroxide (3 mg) was added
  5. stirringthe mixture was stirred for 6 days more
  6. additionMore (3 mg) of lithium hydroxide was added
  7. stirringthe mixture was stirred for 13 days more
  8. customIt was evaporated in vacuum
  9. customto remove THF
  10. extractionextracted with ethyl acetate (×2)
  11. dry with materialdried (magnesium sulphate)
  12. customevaporated

Sources & evidence

ORD record
ord-823cde7ebbf7422f9024e9974a175068
Source dataset
uspto-grants-2008_04
Patent number
US07355069B2

Reaction notes

Loading…