Methanol → 5-Bromo-2,2-dimethylpentan-1-ol

HRID 51093Notes

Reaction equation

HRID 51093 reaction equation
[Li+].[BH4-].CO.[Br:5][CH2:6][CH2:7][CH2:8][C:9]([CH3:16])([CH3:15])[C:10](OCC)=[O:11]>C(Cl)Cl>[Br:5][CH2:6][CH2:7][CH2:8][C:9]([CH3:16])([CH3:15])[CH2:10][OH:11]

Participants

5

Reactant 3

HCID 887MethanolHCID 4148881Lithium borohydrideHCID 10681333Ethyl 5-bromo-2,2-dimethylpentanoate

Product 1

HCID 111831775-Bromo-2,2-dimethylpentan-1-olYield 101.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Under argon, a suspension of LiBH4 (14.8 g, 646 mmol) in methylene chloride (600 mL) was stirred as methanol (25.6 mL, 20.2 g, 629 mmol) was added dropwise, taking care to keep the temperature below 30° C. To this mixture, a solution of ethyl 5-bromo-2,2-dimethylpentanoate (100.0 g, 392 mmol; prepared according to Kuwahara et al. Chem. Pharm. Bull 1997, 48, 1447) in methylene chloride (200 mL) was added dropwise over 20 minutes, and the solution was heated under reflux for 21 h. After chilling in an ice-bath, the reaction was quenched by adding H2O dropwise (100 mL). After the effervescence stopped, 2 N HCl (125 mL) was added dropwise and the solution was stirred until the effervescence ceased. The procedure was repeated with another portion of 2 N HCI (125 mL). The layers were separated, and the aqueous layer was extracted with an additional methylene chloride (500 mL). The two organic portions were combined and washed with 2 N HCl 9300 mL), then sat. NaHCO3 (300 mL). After drying the organics over Na2SO4, the solution was evaporated to yield the product as a light yellow oil (77.6 g, 91% yield). 1H NMR (d6-DMSO), d (ppm): 4.42 (s, 1H); 3.45 (t, 2 H, J=6.6); 3.08 (s, 2H); 1.84-1.69 (m, 2H); 1.27 (t, 2 H, J=8.3); 0.78 (s, 6H). 13C NMR (d6-DMSO), d (ppm): 69.7, 36.9, 35.7, 34.5, 27.4, 24.0.

Workup

  1. additionwas added dropwise
  2. customthe temperature below 30° C
  3. temperaturethe solution was heated
  4. temperatureunder reflux for 21 h
  5. temperatureAfter chilling in an ice-bath
  6. customthe reaction was quenched
  7. additionby adding H2O dropwise (100 mL)
  8. addition2 N HCl (125 mL) was added dropwise
  9. customThe layers were separated
  10. extractionthe aqueous layer was extracted with an additional methylene chloride (500 mL)
  11. washwashed with 2 N HCl 9300 mL), then sat. NaHCO3 (300 mL)
  12. dry with materialAfter drying the organics over Na2SO4
  13. customthe solution was evaporated

Sources & evidence

ORD record
ord-c716edf1cdf24527b83f298e5cee2cce
Source dataset
uspto-grants-2004_03
Patent number
US06713507B2

Reaction notes

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