N,N-Dimethylaniline → (2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)prop-2-enyl diazoacetate

HRID 1179476Notes

Reaction equation

HRID 1179476 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:28][C:29](=[O:38])[O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)[CH:21]=[CH:22][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[CH:22]=[CH:21][C:20]([NH:28][C:29]([O:30][CH2:31][C:32]2[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=2)=[O:38])=[CH:19][C:18]=1[F:17])=[O:14])=[N-:10]

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 8471TriethylamineHCID 11392443benzyl 3-fluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamateHCID 57296158Glyoxylyl Chloride p-toluenesulfonylhydrazone

Product 1

HCID 86600444(2E)-3-(4-{[(benzyloxy)carbonyl]amino}-2-fluorophenyl)prop-2-enyl diazoacetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

Glyoxylic acid chloride p-toluenesulfonylhydrazone (2.2 g, 8.5 mmol, prepared as described by C. J. Blankley, F. J. Sauter and H. O. House, Organic Syntheses, Coll. Vol. V, p. 258; John Wiley, New York (1973)) was added to a suspension of benzyl 3-fluoro-4-[(1E)-3-hydroxyprop-1-enyl]phenylcarbamate (2.14 g, 7.1 mmol) in dichloromethane (55 mL). The mixture was cooled to 0° C. and treated with N,N-dimethylaniline (1.0 mL, 7.81 mmol). After 30 minutes, triethylamine (4.9 mL, 35.5 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 about 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 as a yellow solid.

Workup

  1. concentrationThe reaction mixture was then concentrated to about 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-61e001999f5242c4b00b0f79a17bf3a8
Source dataset
uspto-grants-2007_10
Patent number
US07279494B2

Reaction notes

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