Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylate → Benzyl-4-(3-hydroxy-6-methoxy-2-methyl-1-oxo-4-phenyl-1,2,3,4-tetra-hydroisoquinolin-3-yl)piperidine-1-carboxylate

HRID 17871

Reaction equation

HRID 17871 reaction equation
C(O)(C)C.C(=O)=O.[CH3:8][O:9][C:10]1[CH:19]=[CH:18][C:13]([C:14]([NH:16][CH3:17])=[O:15])=[C:12]([CH2:20][C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[CH:11]=1.C([Li])(CC)C.[CH2:32]([O:39][C:40]([N:42]1[CH2:47][CH2:46][CH:45]([C:48](Cl)=[O:49])[CH2:44][CH2:43]1)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1>C1COCC1.CCCCCC.C(OCC)(=O)C>[CH2:32]([O:39][C:40]([N:42]1[CH2:47][CH2:46][CH:45]([C:48]2([OH:49])[CH:20]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:12]3[C:13](=[CH:18][CH:19]=[C:10]([O:9][CH3:8])[CH:11]=3)[C:14](=[O:15])[N:16]2[CH3:17])[CH2:44][CH2:43]1)=[O:41])[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 2776270Benzyl 4-(chlorocarbonyl)piperidine-1-carboxylateHCID 225559272-Benzyl-4-methoxy-N-methylbenzamideHCID 86586944Isopropanol carbon dioxideHCID 178418400CID 53628100

Product 1

HCID 68433490Benzyl-4-(3-hydroxy-6-methoxy-2-methyl-1-oxo-4-phenyl-1,2,3,4-tetra-hydroisoquinolin-3-yl)piperidine-1-carboxylateYield 49.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 21226206Ethyl acetate hexaneSolvent

Procedure

To an isopropanol/dry ice cooled solution of 4-Methoxy-N-methyl-2-(phenylmethyl)benzamide (250 mg, 0.980 mmol) in THF (50 mL) under argon was added sec-butyllithium solution (1.3M, 1.55 mL, 2.00 mmol) dropwise. After 10 min. a THF (10 mL) solution of benzyl-4-(chlorocarbonyl)piperidine-1-carboxylate (275 mg, 980 mmol) was quickly added to the reaction solution. After 10 min. the reaction was quenched with water then warmed to room temperature. Saturated sodium bicarbonate was added and the resulting mixture extracted with ethyl acetate (3×) and dried with anhydrous magnesium sulfate. Filtration followed by evaporation of solvent in vacuo gave the crude product which was subjected to flash column chromatography (hexane:ethyl acetate 50:50) to afford benzyl-4-(3-hydroxy-6-methoxy-2-methyl-1-oxo-4-phenyl-1,2,3,4-tetra-hydroisoquinolin-3-yl)piperidine-1-carboxylate as a white foam (242 mg, 0.484 mmol, 49%). MS [M+H]+ 501.2

Workup

  1. customAfter 10 min. the reaction was quenched with water
  2. additionSaturated sodium bicarbonate was added
  3. extractionthe resulting mixture extracted with ethyl acetate (3×)
  4. dry with materialdried with anhydrous magnesium sulfate
  5. filtrationFiltration
  6. customfollowed by evaporation of solvent in vacuo
  7. customgave the crude product which

Sources & evidence

ORD record
ord-cdf90ed4d8804be8853d1f11965f5421
Source dataset
uspto-grants-2010_06
Patent number
US07741322B2

Linked notes

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