Water → HCID 72357128, compound

HRID 1394591Notes

Reaction equation

HRID 1394591 reaction equation
[H-].[Na+].[CH3:3][CH2:4][O:5][C:6]([CH:8](P(OCC)(OCC)=O)[F:9])=[O:7].[C:18]([C:21]1[O:25][C:24]2[C:26]([C:30]3[CH:35]=[C:34]([CH:36]([CH3:38])[CH3:37])[CH:33]=[C:32]([CH:39]([CH3:41])[CH3:40])[C:31]=3[O:42][CH2:43][CH:44]([F:46])[F:45])=[CH:27][CH:28]=[CH:29][C:23]=2[CH:22]=1)(=O)[CH3:19].O>CN(C=O)C>[CH2:4]([O:5][C:6](=[O:7])[C:8]([F:9])=[C:18]([C:21]1[O:25][C:24]2[C:26]([C:30]3[CH:35]=[C:34]([CH:36]([CH3:37])[CH3:38])[CH:33]=[C:32]([CH:39]([CH3:41])[CH3:40])[C:31]=3[O:42][CH2:43][CH:44]([F:46])[F:45])=[CH:27][CH:28]=[CH:29][C:23]=2[CH:22]=1)[CH3:19])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 24758Sodium hydrideHCID 2734865Triethyl 2-fluoro-2-phosphonoacetateHCID 17952700HCID 17952700, compound

Product 1

HCID 72357128HCID 72357128, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
40 °C

Procedure

To a slurry of 74 mg (1.54 mmol) of NaH (50% in mineral oil) in 3 mL of dry DMF was added 285.6 mg (1.27 mmol, 2.5 equivalents) of triethyl 2-fluoro-2-phosphonoacetate (diluted in 1 mL of dry DMF) at 0° C. After the gas evolution has ceased, 0.51 mmol of 2-acetyl-7-[3,5-diisopropyl-2-(2,2-difluoroethoxy)phenyl]-benzo[b]furan (see Example 9, step A) diluted in 3 mL of dry DMF was added dropwise. The red mixture was slowly heated to 40° C. until complexion. After cooling, water was added and the solution was extracted 2 times with ethyl acetate. The organic layers were combined, washed with water and brine and dried over MgSO4. After evaporation of the solvents, the crude oil is purified over a short plug of silica gel (eluent: 95/5 hexane/ethyl acetate) to afford 2-fluoro-3-{7-[2-(2,2-difluoroethoxy)-3,5-diisopropylphenyl]-benzo[b]furan-2-yl}-but-2-enoic acid ethyl ester as a pale yellow oil.

Workup

  1. additionwas added dropwise
  2. temperatureAfter cooling
  3. extractionthe solution was extracted 2 times with ethyl acetate
  4. washwashed with water and brine
  5. dry with materialdried over MgSO4
  6. customAfter evaporation of the solvents
  7. customthe crude oil is purified over a short plug of silica gel (eluent: 95/5 hexane/ethyl acetate)

Sources & evidence

ORD record
ord-ee339c1acfc343e18c2159778ca1902b
Source dataset
uspto-grants-2008_03
Patent number
US07348359B2

Reaction notes

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