Pyridine → 4-(2-Cyano-1-methanesulfonyloxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

HRID 1986184Notes

Reaction equation

HRID 1986184 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([OH:19])[CH2:16][C:17]#[N:18])([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].N1C=CC=CC=1.[CH3:26][S:27](Cl)(=[O:29])=[O:28]>ClCCl.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH:15]([O:19][S:27]([CH3:26])(=[O:29])=[O:28])[CH2:16][C:17]#[N:18])([CH3:14])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 3

HCID 1049Pyridine2×HCID 31297Methanesulfonyl chloride2×HCID 688591354-(2-Cyano-1-hydroxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 866253454-(2-Cyano-1-methanesulfonyloxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl esterYield 100%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 4-(2-cyano-1-hydroxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester (4.24 g, 15.8 mmol) and pyridine (3.07 mL, 39.5 mmol) dissolved in dichloromethane (45 mL) at 0° C. is added methanesulfonyl chloride (3.45 mL, 42.6 mmol). After 1 hour, the reaction is not complete and is warmed to room temperature. After 18 hours at room temperature 1 equivalent of pyridine and 1 equivalent of methanesulfonyl chloride is added and stirred for 4 hours. The reaction mixture is diluted with EtOAc and washed several times with saturated NaHCO3. The organic layer is dried over Na2SO4, filtered and concentrated to give crude 4-(2-cyano-1-methanesulfonyloxy-ethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester. Assuming 100% yield, 4-(2-cyano-1-methanesulfonyloxyethyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester (5.47 g, 15.8 mmol) and triethylamine (11.0 mL, 79 mmol) are dissolved in MeOH (60 mL) and heated at 70° C. for 1 hour and concentrated. The residue is dissolved in EtOAc and washed with water, then concentrated and chromatographed using 100% dichloromethane to give cis/trans-4-(2-cyanovinyl)-4-methylpiperidine-1-carboxylic acid tert-butyl ester (3.93 g, 99% yield) as a clear oil.

Workup

  1. washwashed several times with saturated NaHCO3
  2. dry with materialThe organic layer is dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-bd4ad9aa74c147859ee68cf0af3eab45
Source dataset
uspto-grants-2009_06
Patent number
US07547691B2

Reaction notes

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