Diisopropylamine → 1-(2-Benzyloxy-1-hydroxy-ethyl)-cyclohexanecarbonitrile

HRID 429536

Reaction equation

HRID 429536 reaction equation
[Li:1]CCCC.[NH:6]([CH:10]([CH3:12])[CH3:11])[CH:7]([CH3:9])[CH3:8].[CH:13]1([C:19]#[N:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1.[CH2:21]([O:28][CH2:29][CH:30]=[O:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[NH4+].[Cl-]>O1CCCC1>[CH:7]([N-:6][CH:10]([CH3:12])[CH3:11])([CH3:9])[CH3:8].[Li+:1].[CH2:21]([O:28][CH2:29][CH:30]([C:13]1([C:19]#[N:20])[CH2:18][CH2:17][CH2:16][CH2:15][CH2:14]1)[OH:31])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 25517Ammonium ChlorideHCID 69834CyanocyclohexaneHCID 108989(Phenylmethoxy)acetaldehydeHCID 178418339Butyllithium

Product 2

HCID 2724682Lithium diisopropylamideHCID 183883371-(2-Benzyloxy-1-hydroxy-ethyl)-cyclohexanecarbonitrileYield 73%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

Lithium diisopropylamide was prepared by dropwise addition of n-BuLi (2.03 mL; 2.5 M in Hexanes; 5.08 mmol) to a stirred and cooled (−10° C.) solution of i-Pr2NH (0.84 mL; 6.0 mmol) in dry tetrahydrofuran (40 mL). Stirring was continued for 20 minutes. The mixture was cooled to −78° C. and cyclohexane carbonitrile 1 (500 mg; 4.62 mmol) was added over 5 minutes. After a further 30 minutes, benzyloxyacetaldehyde (0.97 mL; 6.93 mmol) was added dropwise. Stirring was continued at −78° C. for 7 hours. The reaction mixture was then allowed to stir overnight at −20° C. Saturated aqueous NH4Cl was added (10 mL), and the mixture was extracted with diethyl ether (2×20° mL), dried over MgSO4 and evaporated. The residue was purified over silica gel chromatography (ether/heptane 1:1) to give 2 as a white solid (872 mg; 3.37 mmol; 73%)

Workup

  1. stirringStirring
  2. waitAfter a further 30 minutes
  3. stirringStirring
  4. waitwas continued at −78° C. for 7 hours
  5. stirringto stir overnight at −20° C
  6. extractionthe mixture was extracted with diethyl ether (2×20° mL)
  7. dry with materialdried over MgSO4
  8. customevaporated
  9. customThe residue was purified over silica gel chromatography (ether/heptane 1:1)

Sources & evidence

ORD record
ord-434f85a4ccee406586eef21d65f7b1b3
Source dataset
uspto-grants-2001_11
Patent number
US06316638B1

Linked notes

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