Tetrahydrofuran → 7-[1-(3-Formylpyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl ester

HRID 412573Notes

Reaction equation

HRID 412573 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]3[CH2:25][CH2:24][NH:23][CH2:22][CH2:21]3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:34]1[CH:39]=[CH:38][N:37]=[CH:36][C:35]=1[CH:40]=[O:41].O1CCCC1>C(O)C.C(OCC)C>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][C:12]([O:18][CH2:19][CH:20]3[CH2:21][CH2:22][N:23]([C:34]4[CH:39]=[CH:38][N:37]=[CH:36][C:35]=4[CH:40]=[O:41])[CH2:24][CH2:25]3)=[CH:13][CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 112794437-(Piperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl esterHCID 140466744-Chloropyridine-3-carbaldehyde

Product 1

HCID 112017967-[1-(3-Formylpyridin-4-yl)piperidin-4-ylmethoxy]-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl esterYield 89.9%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 7-(piperidin-4-ylmethoxy)-1,2,3,4-tetrahydroisoquinoline-2-carboxylic acid tert-butyl ester (442 mg) in ethanol (3 ml) were added triethylamine (0.3 ml) and 4-chloro-3-formylpyridine (Journal of Heterocyclic Chemistry, vol. 25, p. 81 (1988)) (150 mg), and the mixture was stirred under reflux for 27 hours. After completion of the reaction, tetrahydrofuran and diethyl ether were added and insoluble material was removed. The solvent was evaporated and the obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:1) and dried under reduced pressure to give the title compound (430 mg).

Workup

  1. temperatureunder reflux for 27 hours
  2. additionwere added
  3. custominsoluble material was removed
  4. customThe solvent was evaporated
  5. customthe obtained residue was purified by silica gel column chromatography (chloroform:methanol=100:1)
  6. customdried under reduced pressure

Sources & evidence

ORD record
ord-743e528e0052425dbae26fc1138bc4e1
Source dataset
uspto-grants-2003_05
Patent number
US06562828B1

Reaction notes

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