Dimethylformamide → HCID 14539461, compound

HRID 1005929Notes

Reaction equation

HRID 1005929 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[CH:11][C:7]([C:8]([OH:10])=O)=[CH:6][C:5]=1[OH:13].[CH2:14](Br)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1.CN([CH:25]=[O:26])C>C1COCC1.CCOC(C)=O.CCCCCC>[CH2:14]([O:13][C:5]1[CH:6]=[C:7]([CH:11]=[CH:12][C:4]=1[Br:3])[C:8]([O:26][CH2:25][C:4]1[CH:12]=[CH:11][CH:7]=[CH:6][CH:5]=1)=[O:10])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

7

Reactant 4

HCID 6228Dimethylformamide2×HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 64209734-Bromo-3-hydroxybenzoic acid

Product 1

HCID 14539461HCID 14539461, compoundYield 71.5%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent3×HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
9.5 °C

Procedure

To a stirred suspension of NaH (10.47 g, 60% by wt, 0.2616 mol) in THF (1.40 L), at 13.1° C. under argon, was added a solution of 4-bromo-3-hydroxybenzoic acid (28.11 g, 0.130 mol) in THF (400 ml) over 1.25 h maintaining the internal temperature in the range 4-15° C. After 1.5 h a solution of benzyl bromide (44.3 g, 0.2591 mol) in THF (70 ml) was added over 0.5 h. To the resulting suspension was added DMF (500 ml) and the mixture allowed to warm to room temperature. After a further 15 h extra DMF was added (1.5 L) to the suspension. After approximately 30 minutes the reaction mixture was essentially clear and TLC analysis (25% EtOAc/hexane) indicated that effectively all of the starting material had been consumed. The reaction mixture was quenched with dilute ammonium chloride (100 ml) and concentrated in vacuo. To the concentrate was added ethyl acetate (1.0 L) and dilute ammonium chloride (1.0 L) and the fractions separated. The aqueous fraction was back extracted with ethyl acetate (1×450 ml and 1×300 ml). The total organic fraction was dried over sodium sulphate, filtered and concentrated in vacuo. The resulting solid was crystallised from ethanol:water (9:1; vol:vol, 200 ml), heated at reflux, to which was added ethanol (65 ml) until all the material had dissolved. Water was then added dropwise (17 ml), followed by extra ethanol (8.0 ml). The resulting solution was allowed to slowly cool to ambient temperature. The resulting solid was filtered off and dried (44.54 g). This solid was then dissolved in hot ethanol (227 ml) and water (5.0 ml) added and then allowed to slowly cool to ambient temperature. The resulting crystals were filtered off, washed with cold ethanol (25 ml) and dried in a vacuum oven at 50° C. to give the title compound (36.79 g, yield 71.5%). mp=80.5-81.5° C.

Workup

  1. temperatureto warm to room temperature
  2. customhad been consumed
  3. customThe reaction mixture was quenched with dilute ammonium chloride (100 ml)
  4. concentrationconcentrated in vacuo
  5. additionTo the concentrate was added ethyl acetate (1.0 L) and dilute ammonium chloride (1.0 L)
  6. customthe fractions separated
  7. extractionThe aqueous fraction was back extracted with ethyl acetate (1×450 ml and 1×300 ml)
  8. dry with materialThe total organic fraction was dried over sodium sulphate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe resulting solid was crystallised from ethanol:water (9:1; vol:vol, 200 ml)
  12. temperatureheated
  13. temperatureat reflux, to which
  14. additionwas added ethanol (65 ml) until all the material
  15. dissolutionhad dissolved
  16. additionWater was then added dropwise (17 ml)
  17. temperatureto slowly cool to ambient temperature
  18. filtrationThe resulting solid was filtered off
  19. customdried (44.54 g)
  20. dissolutionThis solid was then dissolved in hot ethanol (227 ml)
  21. additionwater (5.0 ml) added
  22. temperatureto slowly cool to ambient temperature
  23. filtrationThe resulting crystals were filtered off
  24. washwashed with cold ethanol (25 ml)
  25. customdried in a vacuum oven at 50° C.

Sources & evidence

ORD record
ord-7a0e63f21eb545cc9de398345e4e572f
Source dataset
uspto-grants-2004_09
Patent number
US06787550B1

Reaction notes

Loading…