Hydrochloric Acid → 1-[3-Bromo-5-(3-hydroxypropyl)phenyl]cyclopropane-1-carbonitrile

HRID 1920861Notes

Reaction equation

HRID 1920861 reaction equation
[Br:1][C:2]1[CH:3]=[C:4](/[CH:13]=[CH:14]/[C:15](OC)=[O:16])[CH:5]=[C:6]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)[CH:7]=1.[BH4-].[Li+].Cl.C([O-])(O)=O.[Na+]>C1COCC1>[Br:1][C:2]1[CH:7]=[C:6]([C:8]2([C:11]#[N:12])[CH2:10][CH2:9]2)[CH:5]=[C:4]([CH2:13][CH2:14][CH2:15][OH:16])[CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4148881Lithium borohydrideHCID 86636473methyl (E)-3-[3-bromo-5-(1-cyanocyclopropyl)phenyl]prop-2-enoate

Product 1

HCID 579696991-[3-Bromo-5-(3-hydroxypropyl)phenyl]cyclopropane-1-carbonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To methyl (E)-3-[3-bromo-5-(1-cyanocyclopropyl)phenyl]prop-2-enoate (590 mg, 1.927 mmol) in THF (15 mL) at 0° C. was added lithium borohydride (125.9 mg, 5.781 mmol). The reaction was allowed to warm to room temperature and stirred overnight. HCl (2M, aq. soln.) was added and the reaction stirred for 5 minutes until the fizzing subsided. NaHCO3 (sat. aq. soln.) was added and the mixture extracted three times with ethyl acetate. The combined organics were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The crude product was purified on silica (Companion, 40 g) eluting with 10-80% EtOAc:Petrol ether to give 1-[3-bromo-5-(3-hydroxypropyl)phenyl]cyclopropane-1-carbonitrile as a yellow oil (64 mg, 67%).

Workup

  1. stirringthe reaction stirred for 5 minutes until the fizzing
  2. extractionthe mixture extracted three times with ethyl acetate
  3. washThe combined organics were washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified on silica (Companion, 40 g)
  8. washeluting with 10-80% EtOAc

Sources & evidence

ORD record
ord-e6f61fb5a74f4739a2508618b636ee5a
Source dataset
uspto-grants-2012_05
Patent number
US08173635B2

Reaction notes

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