Butyl vinyl ether → Methyl 2-acetyl-4-methoxybenzoate

HRID 1471349Notes

Reaction equation

HRID 1471349 reaction equation
Br[C:2]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH:14]([O:16]CCCC)=[CH2:15].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CCN(CC)CC>CC#N.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[C:14]([C:2]1[CH:11]=[C:10]([O:12][CH3:13])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])(=[O:16])[CH3:15]

Participants

8

Reactant 4

HCID 8108Butyl vinyl etherHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 15110997Methyl 2-bromo-4-methoxybenzoate

Product 1

HCID 59373125Methyl 2-acetyl-4-methoxybenzoateYield 96.5%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
97 °C

Procedure

A mixture of methyl 2-bromo-4-methoxybenzoate (4) (5.9 g, 23.9 mmol), butyl vinyl ether (15.4 mL, 119.4 mmol), Ph3P (939.0 mg, 3.6 mmol), Et3N (4.3 mL, 31.0 mmol), and Pd(OAc)2 (343.0 mg, 1.8 mmol) in MeCN (45 mL) is stirred under argon at 97° C. for 18 h, cooled to room temperature, diluted with H2O (50 mL), and filtered through Celite® (H2O rinse). The filtrate is concentrated to dryness at reduced pressure. The residue plus tetrahydrofuran (140 mL) and 10% HCl (140 mL) were stirred for 2 h. After tetrahydrofuran removal at reduced pressure, the residue is extracted with dichloromethane (3×70 mL). The extract is washed (brine) and dried. After solvent removal at reduced pressure, the residue is purified on silica gel (16.7% to 33.3% ethyl acetate/hexane) to give 4.8 g (96%) of 5 as a yellow solid, mp 48-50° C. IR 2962, 1733, 1688, 1258 cm−1; 1H NMR (CDCl3) δ 2.50 (s, 3H, CH3CO), 3.86 (s, 6H, CH3O, CO2CH3), 6.76 (d, J=2.0 Hz, 1H, 3-PhH), 6.93 (dd, J=7.2, 2.0 Hz, 1H, 5-PhH), 7.90 ppm (d, J=7.2 Hz, 1H, 6-PhH).

Workup

  1. temperaturecooled to room temperature
  2. filtrationfiltered through Celite® (H2O rinse)
  3. concentrationThe filtrate is concentrated to dryness at reduced pressure
  4. stirringThe residue plus tetrahydrofuran (140 mL) and 10% HCl (140 mL) were stirred for 2 h
  5. customAfter tetrahydrofuran removal at reduced pressure
  6. extractionthe residue is extracted with dichloromethane (3×70 mL)
  7. washThe extract is washed (brine)
  8. customdried
  9. customAfter solvent removal at reduced pressure
  10. customthe residue is purified on silica gel (16.7% to 33.3% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-a72be85c9ef845929bbbc6b4bd5784b1
Source dataset
uspto-grants-2015_04
Patent number
US09012217B2

Reaction notes

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