Methyl iodide → Tert-butyl 4-methoxypiperidine-1-carboxylate

HRID 2353140Notes

Reaction equation

HRID 2353140 reaction equation
ClC1N=C(N2CCOCC2)C2SC(CN3CCC([CH2:18][O:19]C)CC3)=CC=2N=1.COCC1CCNCC1.[C:36]([O:40][C:41]([N:43]1[CH2:48][CH2:47][CH:46](CO)[CH2:45][CH2:44]1)=[O:42])([CH3:39])([CH3:38])[CH3:37].[H-].[Na+].CI>C1COCC1>[C:36]([O:40][C:41]([N:43]1[CH2:44][CH2:45][CH:46]([O:19][CH3:18])[CH2:47][CH2:48]1)=[O:42])([CH3:37])([CH3:38])[CH3:39]

Participants

7

Reactant 5

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 2764081Tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylateHCID 47152834-(Methoxymethyl)piperidineHCID 57494023HCID 57494023, compound

Product 1

HCID 21955381Tert-butyl 4-methoxypiperidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

Via 2-Chloro-6-(4-methoxymethyl-piperidin-1-ylmethyl)-4-morpholin-4-yl-thieno[3,2-d]pyrimidine, prepared from 4-methoxymethyl-piperidine. Amine preparation: To a solution of 4-hydroxymethyl-piperidine-1-carboxylic acid tert-butyl ester (212 mg) stirring in dry THF (10 mL) under a nitrogen atmosphere was added sodium hydride (60% in paraffin oil; 45 mg) followed after 20 min by methyl iodide and the reaction mixture was warmed to 70° C. After 4 h the mixture was cooled and quenched with water (10 mL) extracted into ethyl acetate, and dried (MgSO4). The residue was purified using flash chromatography to yield 4-methoxy-piperidine-1-carboxylic acid tert-butyl ester (158 mg) as a colourless oil. Treatment with TFA yielded the desired amine which was isolated as the TFA salt.

Workup

  1. temperatureAfter 4 h the mixture was cooled
  2. customquenched with water (10 mL)
  3. extractionextracted into ethyl acetate
  4. dry with materialdried (MgSO4)
  5. customThe residue was purified

Sources & evidence

ORD record
ord-ec36a4434e7548df8b3fca28379dd1a4
Source dataset
uspto-grants-2010_07
Patent number
US07750002B2

Reaction notes

Loading…