Hydrochloric Acid → (1-Hydroxycyclohexyl)(4-methoxyphenyl)acetonitrile

HRID 2249304Notes

Reaction equation

HRID 2249304 reaction equation
C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][C:23]#[N:24])=[CH:18][CH:17]=1.[C:25]1(=[O:31])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1.Cl>CCCCCC.C(NC(C)C)(C)C.C1(C)C=CC=CC=1.O>[OH:31][C:25]1([CH:22]([C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)[C:23]#[N:24])[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]1

Participants

10

Reactant 5

HCID 313Hydrochloric AcidHCID 7967CyclohexanoneHCID 66031Benzeneacetonitrile, 4-methoxy-HCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Product 1

HCID 9899621(1-Hydroxycyclohexyl)(4-methoxyphenyl)acetonitrileYield 79.1%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 1140TolueneSolvent3×HCID 7912DiisopropylamineSolventHCID 8058HexaneSolvent

Procedure

Lithium diisopropylamide was made from 1.6M butyl lithium in hexane (325 ml), diisopropylamine (73 ml) and toluene (300 ml) under an inert atmosphere of nitrogen. A solution of p-methoxyphenylacetonitrile (76.5 g) in toluene (75 ml) was added to the solution under nitrogen over 15 minutes whilst the internal temperature was maintained below 10° C. After a half hour a solution of cyclohexanone (46 g) in toluene (50 ml) was added over 15 minutes to the reaction mixture under nitrogen whilst the internal temperature was maintained below 10° C. After a further half hour the mixture was blown over onto an ice-cold mixture of 12N hydrochloric acid (100 ml) and water (1l). The crystalline material was filtered off and then taken up into dichloromethane. The solution was washed with water and dried. The solvent was replaced with di-isopropyl ether by distillation. After cooling, the product was filtered and dried in vacuo to yield 91 g (79% yield ) of the title compound.

Workup

  1. temperaturewas maintained below 10° C
  2. temperaturewas maintained below 10° C
  3. filtrationThe crystalline material was filtered off
  4. washThe solution was washed with water
  5. customdried
  6. distillationThe solvent was replaced with di-isopropyl ether by distillation
  7. temperatureAfter cooling
  8. filtrationthe product was filtered
  9. customdried in vacuo

Sources & evidence

ORD record
ord-4b21ea9e847b4399a1f756204491ed39
Source dataset
uspto-grants-1991_08
Patent number
US05043466

Reaction notes

Loading…