4-Hydroxybenzaldehyde → Methyl 5-[4-formylphenoxy)-2,2-dimethyl-pentanoate

HRID 986678Notes

Reaction equation

HRID 986678 reaction equation
[OH:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=[O:7])=[CH:4][CH:3]=1.[H-].[Na+].Br[CH2:13][CH2:14][CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19][CH3:20])=[O:18]>CN(C)C=O>[CH:6]([C:5]1[CH:8]=[CH:9][C:2]([O:1][CH2:13][CH2:14][CH2:15][C:16]([CH3:22])([CH3:21])[C:17]([O:19][CH3:20])=[O:18])=[CH:3][CH:4]=1)=[O:7]

Participants

5

Reactant 3

HCID 1264-HydroxybenzaldehydeHCID 24758Sodium hydrideHCID 13050502Methyl 5-bromo-2,2-dimethylpentanoate

Product 1

HCID 15599127Methyl 5-[4-formylphenoxy)-2,2-dimethyl-pentanoate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A solution of 48.9 g (0.4 mol) of 4-hydroxybenzaldehyde in 600 ml of dimethylformamide was stirred under a nitrogen atmosphere. Sodium hydride (31.2 g; 0.44 mol) was added to the stirring solution over 45 minutes. The temperature of the reaction mixture was maintained at 35°-40° during the addition, and stirring was continued for an additional 45 minutes at room temperature. Methyl 5-bromo-2,2-dimethylpentanoate (98.1 g; 0.44 mol), was added dropwise over 20 minutes. The reaction temperature was maintained at 40° during the addition. After addition was complete, the temperature was raised to 65° C. and stirring was continued at 65° C. for 31/2 hours. After standing overnight, the dimethylformamide was removed on a rotary evaporator and the residue was taken up in water and ether. The aqueous layer was extracted a second time with ether and the combined extracts were washed, dried, and concentrated under reduced pressure. The residue was triturated two times with n-heptane. The heptane insoluble oil was distilled via a short path apparatus to give methyl 5-[4-formylphenoxy)-2,2-dimethyl-pentanoate: bp 143°-144° C. at 0.03 mm of Hg; yield 39.4 g (37%). Additional analytically pure product was obtained from the heptane extract: 32.3 g (31%). Anal. Calcd. for C15H20O4 :

Workup

  1. temperatureThe temperature of the reaction mixture was maintained at 35°-40° during the addition
  2. temperatureThe reaction temperature was maintained at 40° during the addition
  3. additionAfter addition
  4. stirringstirring
  5. customwas continued at 65° C. for 31
  6. custom2 hours
  7. waitAfter standing overnight
  8. customthe dimethylformamide was removed on a rotary evaporator
  9. extractionThe aqueous layer was extracted a second time with ether
  10. washthe combined extracts were washed
  11. customdried
  12. concentrationconcentrated under reduced pressure
  13. customThe residue was triturated two times with n-heptane
  14. distillationThe heptane insoluble oil was distilled via a short path apparatus

Sources & evidence

ORD record
ord-de710e54c47e432c9e53fa6eba8d61df
Source dataset
uspto-grants-1987_12
Patent number
US04714762

Reaction notes

Loading…