4-Methylcyclohexanone → 1-{6-[(Tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol

HRID 734866Notes

Reaction equation

HRID 734866 reaction equation
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][C:10]([C:13]#[C:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])=[N:11][CH:12]=1.[CH3:22][CH:23]1[CH2:28][CH2:27][C:26](=[O:29])[CH2:25][CH2:24]1.[Cl-].[NH4+]>C(OCC)C.C1COCC1.CCOC(C)=O>[Si:15]([C:14]#[C:13][C:10]1[N:11]=[CH:12][C:7]([C:26]2([OH:29])[CH2:27][CH2:28][CH:23]([CH3:22])[CH2:24][CH2:25]2)=[CH:8][CH:9]=1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

8

Reactant 4

HCID 115254-MethylcyclohexanoneHCID 25517Ammonium ChlorideHCID 666112135-Bromo-2-((tert-butyldimethylsilyl)ethynyl)pyridineHCID 178418339Butyllithium

Product 1

HCID 690576181-{6-[(Tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

9.5 mL (16.19 mmol) of n-BuLi (1.6 M in THF) was slowly added under argon at −70° C. to a solution of 4.50 g (15.19 mmol) of 5-bromo-2-[(tert-butyldimethylsilanyl)ethynyl]pyridine in 50 mL of diethyl ether and 60 mL of THF and after the addition had ended the mixture was stirred for another 2 minutes. 1.86 mL (15.19 mmol) of 4-methylcyclohexanone was added and the mixture was slowly heated to RT. 150 mL of saturated aqueous ammonium chloride solution were added and the aqueous phase was exhaustively extracted with EtOAc. The combined organic extracts were with washed with semisaturated aqueous sodium bicarbonate solution, dried over magnesium sulfate, and evaporated down in vacuo. The residue was purified by chromatography (silica gel, PE/EtOAc 4:1). 2 fractions were isolated. Fraction 1: cis-1-{6-[(tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol; yield: 1.40 g (28% of theoretical); C20H31NOSi (M=329.552); calc.: molpeak (M+H)+: 330; found: molpeak (M+H)+: 330; Rf value: 0.40 (silica gel, PE/EtOAc 4:1). Fraction 2: trans-1-{6-[(tert-butyldimethylsilanyl)ethynyl]pyridin-3-yl}-4-methylcyclohexanol; yield: 1.00 g (20% of theoretical); C20H31NOSi (M=329.552); calc.: molpeak (M+H)+: 330; found: molpeak (M+H)+: 330; Rf value: 0.30 (silica gel, PE/EtOAc 4:1).

Workup

  1. additionafter the addition
  2. extractionthe aqueous phase was exhaustively extracted with EtOAc
  3. washwith washed with semisaturated aqueous sodium bicarbonate solution
  4. dry with materialdried over magnesium sulfate
  5. customevaporated down in vacuo
  6. customThe residue was purified by chromatography (silica gel, PE/EtOAc 4:1)
  7. custom2 fractions were isolated

Sources & evidence

ORD record
ord-d79ba20ef49b489292aa06284fcf08c1
Source dataset
uspto-grants-2009_09
Patent number
US07592358B2

Reaction notes

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