N,N-Dimethylaniline → (2e)-3-{2,6-Difluoro-4-[(isopropoxycarbonyl)amino]phenyl}prop-2-enyl diazoacetate

HRID 1179482Notes

Reaction equation

HRID 1179482 reaction equation
C1(C)C=CC(S([NH:10][N:11]=[CH:12][C:13](Cl)=[O:14])(=O)=O)=CC=1.[F:17][C:18]1[CH:19]=[C:20]([NH:29][C:30](=[O:35])[O:31][CH:32]([CH3:34])[CH3:33])[CH:21]=[C:22]([F:28])[C:23]=1/[CH:24]=[CH:25]/[CH2:26][OH:27].CN(C)C1C=CC=CC=1.C(N(CC)CC)C>ClCCl>[N+:11](=[CH:12][C:13]([O:27][CH2:26]/[CH:25]=[CH:24]/[C:23]1[C:18]([F:17])=[CH:19][C:20]([NH:29][C:30]([O:31][CH:32]([CH3:33])[CH3:34])=[O:35])=[CH:21][C:22]=1[F:28])=[O:14])=[N-:10]

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 8471TriethylamineHCID 57296158Glyoxylyl Chloride p-toluenesulfonylhydrazoneHCID 58978084isopropyl 3,5-difluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate

Product 1

HCID 131726632(2e)-3-{2,6-Difluoro-4-[(isopropoxycarbonyl)amino]phenyl}prop-2-enyl diazoacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Glyoxylic acid chloride p-toluenesulfonylhydrazone (4.64 g, 17.8 mmol) was added to a suspension of isopropyl 3,5-difluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate (2.68 g, 9.89 mmol) in dichloromethane (66 mL). The mixture was cooled to 0° C. and treated with N,N-dimethylaniline (2.26 mL, 17.8 mmol). After 30 minutes, triethylamine (6.89 mL, 49.5 mmol) was added and the mixture stirred 30 minutes at 0° C. and 15 minutes at room temperature. The reaction mixture was then concentrated to ca. 15 mL and 50 mL of water added. The mixture was extracted with two portions of diethyl ether and the combined organic solutions washed with saturated NaHCO3, brine, and dried (MgSO4), filtered and concentrated. Purification by column chromatography (0-25% ethyl acetate-hexane) provided the title compound a yellow solid.

Workup

  1. concentrationThe reaction mixture was then concentrated to ca. 15 mL and 50 mL of water
  2. additionadded
  3. extractionThe mixture was extracted with two portions of diethyl ether
  4. washthe combined organic solutions washed with saturated NaHCO3, brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by column chromatography (0-25% ethyl acetate-hexane)

Sources & evidence

ORD record
ord-17a464035f7b48108458ace76583064d
Source dataset
uspto-grants-2007_10
Patent number
US07279494B2

Reaction notes

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