Diethyl Ether → 2-Benzyloxycarbonylamino-3-(2,6-difluorophenyl)acrylic acid methyl ester

HRID 2212214Notes

Reaction equation

HRID 2212214 reaction equation
[CH3:1][O:2][C:3]([CH:5](P(OC)(OC)=O)[NH:6][C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])=[O:4].N12CCCN=C1CCCCC2.[F:34][C:35]1[CH:42]=[CH:41][CH:40]=[C:39]([F:43])[C:36]=1[CH:37]=O.C(OCC)C>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:4])[C:5]([NH:6][C:7]([O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:8])=[CH:37][C:36]1[C:35]([F:34])=[CH:42][CH:41]=[CH:40][C:39]=1[F:43]

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 1362842,6-DifluorobenzaldehydeHCID 2734718Methyl 2-{[(benzyloxy)carbonyl]amino}-2-(dimethyl phosphono)acetate

Product 1

HCID 673920002-Benzyloxycarbonylamino-3-(2,6-difluorophenyl)acrylic acid methyl esterYield 72%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

N-(Benzyloxycarbonyl)-α-phosphonoglycine trimethyl ester (Aldrich No. 37,635-3; 6.7 g, 20 mmol) and 1,8-diazabicyclo[5,4,0]undec-7-ene (Aldrich No. 13, 900-9; 3.3 mL, 22 mmol) were dissolved in methylene chloride (11 mL) and stirred at room temperature for 15 min., and then cooled to <−30° C. A solution of 2,6-difluorobenzaldehyde (1.9 mL, 20 mmol) in methylene chloride (25 mL) was added to the reaction mixture dropwise over 20 min. The reaction mixture was stirred for another 20 min., and then allowed to warm up to room temperature for 30 min. The reaction mixture was then poured into ethyl ether (300 mL) and washed with 1 N HCl, brine and dried over MgSO4. Rotary evaporation gave 2-benzyloxycarbonylamino-3-(2,6-difluorophenyl)acrylic acid methyl ester. This crude product was purified by chromatography on a Medium Pressure Liquid Column (MPLC) eluting with 20% ethyl acetate/80% hexane to give pure product (5 g, 72% yield, liquid).

Workup

  1. temperaturecooled to <−30° C
  2. stirringThe reaction mixture was stirred for another 20 min.
  3. temperatureto warm up to room temperature for 30 min
  4. washwashed with 1 N HCl, brine
  5. dry with materialdried over MgSO4
  6. customRotary evaporation

Sources & evidence

ORD record
ord-ec76768d6faa4087aef55b65a00097fa
Source dataset
uspto-grants-2006_09
Patent number
US07101880B2

Reaction notes

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