Isobutylamine → (RS)-(2,6-difluoro-4-isobutylcarbamoyl-phenyl)-ethoxy-acetic acid ethyl ester

HRID 1247375Notes

Reaction equation

HRID 1247375 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[CH2:13]([O:15][CH:16]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[C:17]1[C:25]([F:26])=[CH:24][C:20]([C:21]([OH:23])=O)=[CH:19][C:18]=1[F:27])[CH3:14].[CH2:33]([NH2:37])[CH:34]([CH3:36])[CH3:35].CCOC(C)=O>C1COCC1>[CH2:31]([O:30][C:28](=[O:29])[CH:16]([C:17]1[C:18]([F:27])=[CH:19][C:20]([C:21](=[O:23])[NH:37][CH2:33][CH:34]([CH3:36])[CH3:35])=[CH:24][C:25]=1[F:26])[O:15][CH2:13][CH3:14])[CH3:32]

Participants

6

Reactant 4

HCID 6558IsobutylamineHCID 8857Ethyl AcetateHCID 682631,1'-CarbonyldiimidazoleHCID 21904951(RS)-4-(ethoxy-ethoxycarbonyl-methyl)-3,5-difluoro-benzoic acid

Product 1

HCID 69291808(RS)-(2,6-difluoro-4-isobutylcarbamoyl-phenyl)-ethoxy-acetic acid ethyl esterYield 67.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1,1′-Carbonyldiimidazole (88 mg) was dissolved in THF (1 ml) and a solution of (RS)-4-(ethoxy-ethoxycarbonyl-methyl)-3,5-difluoro-benzoic acid (156 mg) in THF (1 ml) was added. After 30 min stirring at rt isobutylamine (41 mg) was added and the mixture was stirred 3 h. AcOEt (20 ml) was added and the solution was washed with 1 N HCl (20 ml). The aqueous layer was extracted with two more portions AcOEt (20 ml), the the combined organic layers were dried (Na2SO4) and the solvent was evaporated. CC (Hept/AcOET 3:1) afforded 125 mg (67%) of (RS)-(2,6-difluoro-4-isobutylcarbamoyl-phenyl)-ethoxy-acetic acid ethyl ester. White solid.

Workup

  1. additionwas added
  2. washthe solution was washed with 1 N HCl (20 ml)
  3. extractionThe aqueous layer was extracted with two more portions AcOEt (20 ml)
  4. dry with materialthe the combined organic layers were dried (Na2SO4)
  5. customthe solvent was evaporated

Sources & evidence

ORD record
ord-dac827e433f248cba366bcd93b71ed67
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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