Water → 4-(1-Hydroxycyclobutyl)benzonitrile

HRID 844003Notes

Reaction equation

HRID 844003 reaction equation
Br[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=1.[Li]CCCC.[C:15]1(=[O:19])[CH2:18][CH2:17][CH2:16]1.O>O1CCCC1>[OH:19][C:15]1([C:2]2[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[CH:4][CH:3]=2)[CH2:18][CH2:17][CH2:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 12162Benzonitrile, 4-bromo-HCID 14496CyclobutanoneHCID 178418339Butyllithium

Product 1

HCID 224816304-(1-Hydroxycyclobutyl)benzonitrileYield 78.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-100 °C

Procedure

To a solution of 4-Bromo-benzonitrile (2.0 grams, 10.99 mmole) in tetrahydrofuran (30 ml) at −100° C. was added dropwise 2.5 M nBuLi (4.8 ml) and stirred at −100° C. for 15 minutes. Cyclobutanone (0.965 grams, 13.19 mmole) was added dropwise and stirred for 10 minutes and allowed to warm to room temperature over 1 hour. The mixture was poured into 200 ml water and extracted with diethyl ether. The combined extracts were washed with water and brine, dried over MgSO4, filtered, and concentrated to an oil which was purified via flash chromatography on silica using 40% ethyl acetate/hexane as eluent to give a clear oil (1.5 g). MW 173.23; MS (m/e) 173 (M+).

Workup

  1. stirringstirred for 10 minutes
  2. temperatureto warm to room temperature over 1 hour
  3. extractionextracted with diethyl ether
  4. washThe combined extracts were washed with water and brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated to an oil which
  8. customwas purified via flash chromatography on silica using 40% ethyl acetate/hexane as eluent

Sources & evidence

ORD record
ord-790966719e514df0b4c6b1e6df086318
Source dataset
uspto-grants-2002_04
Patent number
US06380218B1

Reaction notes

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