4-Fluorophenylhydrazine hydrochloride → 6-O-tert-butyl 4a-O-methyl 1-(4-fluorophenyl)-4,5,7,8-tetrahydropyrazolo(3,4-g)isoquinoline-4a,6-dicarboxylate

HRID 1907273Notes

Reaction equation

HRID 1907273 reaction equation
[CH3:1][O:2][C:3]([C@@:5]12[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:21])([CH3:20])[CH3:19])=[O:16])[CH2:12][CH2:11][C:10]1=[CH:9][C:8](=O)/[C:7](=[CH:23]\O)/[CH2:6]2)=[O:4].Cl.[F:26][C:27]1[CH:32]=[CH:31][C:30]([NH:33][NH2:34])=[CH:29][CH:28]=1.C([O-])(=O)C.[Na+]>C(O)(=O)C>[CH3:1][O:2][C:3]([C@@:5]12[CH2:14][N:13]([C:15]([O:17][C:18]([CH3:19])([CH3:21])[CH3:20])=[O:16])[CH2:12][CH2:11][C:10]1=[CH:9][C:8]1[N:33]([C:30]3[CH:31]=[CH:32][C:27]([F:26])=[CH:28][CH:29]=3)[N:34]=[CH:23][C:7]=1[CH2:6]2)=[O:4]

Participants

5

Reactant 3

HCID 699814-Fluorophenylhydrazine hydrochlorideHCID 517045Sodium AcetateHCID 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 583333606-O-tert-butyl 4a-O-methyl 1-(4-fluorophenyl)-4,5,7,8-tetrahydropyrazolo(3,4-g)isoquinoline-4a,6-dicarboxylateYield 76.8%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of (R)-7-[1-hydroxymeth-(Z)-ylidene]-6-oxo-4,6,7,8-tetrahydro-3H-isoquinoline-2,8a-dicarboxylic acid 2-tert-butyl ester 8a-methyl ester (3.8 g), 4-fluorophenylhydrazine hydrochloride (2.7 g), sodium acetate (1.4 g) and acetic acid (30 mL) was stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure, and the residue was partitioned between diethyl ether and 2.0 M aqueous hydrochloric acid solution. The organic phase was washed with water, aqueous potassium carbonate solution and brine, and then dried over sodium sulfate. The solvent was removed under reduced pressure, and the residue was triturated with a mixture of cyclohexane and diethyl ether to afford the title compound as a yellow solid (3.7 g). 1H NMR (CDCl3): δ 7.48-7.39 (m, 3H), 7.21-7.12 (m, 2H), 6.45-6.41 (s, 1H), 4.69-4.55 (d, 1H, J=13 Hz), 4.32-3.98 (m, 1H), 3.64 (s, 3H), 3.51-3.33 (m, 1H), 3.00-2.71 (m, 3H), 2.59-2.51 (d, 1H, J=16 Hz), 2.48-2.34 (m, 1H), 1.46 (s, 9H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure
  2. customthe residue was partitioned between diethyl ether and 2.0 M aqueous hydrochloric acid solution
  3. washThe organic phase was washed with water, aqueous potassium carbonate solution and brine
  4. dry with materialdried over sodium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue was triturated with a mixture of cyclohexane and diethyl ether

Sources & evidence

ORD record
ord-0e9fad8c29744cc6a344c63052cc7a57
Source dataset
uspto-grants-2013_12
Patent number
US08598154B2

Reaction notes

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