Water → (R)-6-tert-butyl 4a-methyl 1-phenyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-4a,6(4H)-dicarboxylate

HRID 920630Notes

Reaction equation

HRID 920630 reaction equation
O/[CH:2]=[C:3]1\[C:4](=O)[CH:5]=[C:6]2[C@:11]([C:13]([O:15][CH3:16])=[O:14])([CH2:12]\1)[CH2:10][N:9]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:8][CH2:7]2.O.O.O.C([O-])(=O)C.[Na+].[C:33]1([NH:39][NH2:40])[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.O>C(O)(=O)C.ClCCl>[C:33]1([N:39]2[C:4]3[CH:5]=[C:6]4[C@:11]([C:13]([O:15][CH3:16])=[O:14])([CH2:12][C:3]=3[CH:2]=[N:40]2)[CH2:10][N:9]([C:17]([O:19][C:20]([CH3:21])([CH3:23])[CH3:22])=[O:18])[CH2:8][CH2:7]4)[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1

Participants

7

Reactant 4

HCID 962WaterHCID 7516PhenylhydrazineHCID 23665404Sodium Acetate TrihydrateHCID 58333286(R,Z)-2-tert-butyl 8a-methyl 7-(hydroxymethylene)-6-oxo-3,4,6,7,8,8a-hexahydroisoquinoline-2,8a(1H)-dicarboxylate

Product 1

HCID 86709991(R)-6-tert-butyl 4a-methyl 1-phenyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-4a,6(4H)-dicarboxylateYield 52.5%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

(R,Z)-2-tert-butyl 8a-methyl 7-(hydroxymethylene)-6-oxo-3,4,6,7,8,8a-hexahydroisoquinoline-2,8a(1H)-dicarboxylate (1.09 g, 3.23 mmol) was suspended in acetic acid (20 mL), and sodium acetate trihydrate (0.265 g, 3.23 mmol) and phenylhydrazine (0.318 ml, 3.23 mmol) were added. The reaction mixture was stirred at room temperature for 30 minutes, then water (20 mL) and dichloromethane (20 mL) were added and the phases were separated via a phase separator. The solvent was removed to give an orange oil. The crude product was purified by chromatography on silica gel (gradient: 0-50% ethyl acetate in isohexane) to afford (R)-6-tert-butyl 4a-methyl 1-phenyl-4a,5,7,8-tetrahydro-1H-pyrazolo[3,4-g]isoquinoline-4a,6(4H)-dicarboxylate (694 mg) as a pale yellow solid. LCMS (Method F, ES-API): RT 2.48 min, m+H=410.

Workup

  1. customthe phases were separated via a phase separator
  2. customThe solvent was removed
  3. customto give an orange oil
  4. customThe crude product was purified by chromatography on silica gel (gradient: 0-50% ethyl acetate in isohexane)

Sources & evidence

ORD record
ord-286bf727f0ad4ee3b046643c85c7a975
Source dataset
uspto-grants-2016_03
Patent number
US09273047B2

Reaction notes

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