Butyl vinyl ether → Methyl 2-acetyl-5-methoxybenzoate

HRID 1471341Notes

Reaction equation

HRID 1471341 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([O:12][CH3:13])=[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]=[CH:10][C:9]([O:12][CH3:13])=[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 2776849Methyl 2-bromo-5-methoxybenzoate

Product 1

HCID 59373119Methyl 2-acetyl-5-methoxybenzoateYield 99.6%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
99 °C

Procedure

A mixture of methyl 2-bromo-5-methoxybenzoate (1) (5.0 g, 20.4 mmol), butyl vinyl ether (13.1 mL, 102.0 mmol), Ph3P (802.3 mg, 3.1 mmol), Et3N (3.7 mL, 26.5 mmol), and Pd(OAc)2 (343.0 mg, 1.5 mmol) in MeCN (40 mL) is stirred under argon at 99° C. for 16.5 h and then cooled to room temperature. The residue is diluted with H2O (50 mL), and the resultant suspension is filtered through Celite® (H2O rinse). The filtrate is concentrated to dryness at reduced pressure. To the residue is added tetrahydrofuran (125 mL) and 10% HCl (125 mL). The mixture is stirred for 2 h before the tetrahydrofuran is removed at reduced pressure. This residue is extracted with ethyl acetate (100 mL, 70 mL, and 60 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 4.23 g (99%) of 2 as a yellow liquid. IR 2958, 1730, 1683, 1270 cm−1; 1H NMR (CDCl3) δ 2.55 (s, 3H, CH3CO), 3.90 (s, 3H, CH3O), 3.94 (s, 3H, CO2CH3), 7.04 (dd, J=8.7, 2.7 Hz, 1H, 4-PhH), 7.17 (d, J=2.7 Hz, 1H, 6-PhH), 7.61 ppm (d, J=8.7 Hz, 1H, 3-PhH).

Workup

  1. temperaturecooled to room temperature
  2. filtrationthe resultant suspension is filtered through Celite® (H2O rinse)
  3. concentrationThe filtrate is concentrated to dryness at reduced pressure
  4. additionTo the residue is added tetrahydrofuran (125 mL) and 10% HCl (125 mL)
  5. stirringThe mixture is stirred for 2 h before the tetrahydrofuran
  6. customis removed at reduced pressure
  7. extractionThis residue is extracted with ethyl acetate (100 mL, 70 mL, and 60 mL)
  8. washThe extract is washed (brine)
  9. customdried
  10. customAfter solvent removal at reduced pressure
  11. customthe residue is purified on silica gel (16.7% to 33.3% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-009de23dcdc3478ca1f1f6c9e8ccccf3
Source dataset
uspto-grants-2015_04
Patent number
US09012217B2

Reaction notes

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