Triethylamine → (+/-)-2-Bromobutyric acid, 2,6-dimethoxy-4-methylphenyl ester

HRID 1280829Notes

Reaction equation

HRID 1280829 reaction equation
[Br:1][CH:2]([CH2:6][CH3:7])[C:3](Br)=[O:4].[CH3:8][O:9][C:10]1[CH:15]=[C:14]([CH3:16])[CH:13]=[C:12]([O:17][CH3:18])[C:11]=1[OH:19].C(N(CC)CC)C>ClCCl>[Br:1][CH:2]([CH2:6][CH3:7])[C:3]([O:19][C:11]1[C:12]([O:17][CH3:18])=[CH:13][C:14]([CH3:16])=[CH:15][C:10]=1[O:9][CH3:8])=[O:4]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 1172932-Bromobutanoyl bromideHCID 2409254-Methyl-2,6-dimethoxyphenol

Product 1

HCID 10852931(+/-)-2-Bromobutyric acid, 2,6-dimethoxy-4-methylphenyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

2-Bromobutyryl bromide (31.1 ml) was added to a stirred solution of 2,6-dimethoxy-4-methylphenol (45 g) in dry dichloromethane (500 ml), whereupon triethylamine (37.3 ml) was added dropwise over 30 minutes, maintaining the internal temperature below 10° C. using an ice-salt bath. During the addition a white precipitate formed. After addition was complete the reaction mixture was stirred for 1.5 hours, then filtered. The solid was washed with diethyl ether (200 ml) and the filtrate washed twice with saturated sodium bicarbonate solution (100 ml). The organic phase was dried over magnesium sulphate, filtered and the solvent removed under reduced pressure to give the crude product as an oil (79.4 g). To remove any residual starting phenol, the oil was dissolved in diethyl ether and washed with sodium hydroxide solution (0.1 M; 3×100 ml), then water (4×100 ml). The organic phase was dried over magnesium sulphate, filtered and the solvent removed under reduced pressure to give the title compound as a yellow oil (72.9 g).

Workup

  1. additionwas added dropwise over 30 minutes
  2. temperaturemaintaining the internal temperature below 10° C.
  3. additionDuring the addition a white precipitate
  4. customformed
  5. additionAfter addition
  6. filtrationfiltered
  7. washThe solid was washed with diethyl ether (200 ml)
  8. washthe filtrate washed twice with saturated sodium bicarbonate solution (100 ml)
  9. dry with materialThe organic phase was dried over magnesium sulphate
  10. filtrationfiltered
  11. customthe solvent removed under reduced pressure
  12. customto give the crude product as an oil (79.4 g)
  13. customTo remove
  14. dissolutionthe oil was dissolved in diethyl ether
  15. washwashed with sodium hydroxide solution (0.1 M; 3×100 ml)
  16. dry with materialThe organic phase was dried over magnesium sulphate
  17. filtrationfiltered
  18. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-714368328d2e4cc18888e6aa4e199753
Source dataset
uspto-grants-2002_09
Patent number
US06451854B1

Reaction notes

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