Water → 9-tert-butyl-2-fluoro-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-one

HRID 1971759Notes

Reaction equation

HRID 1971759 reaction equation
[C:1]([N:5]1[CH2:26][CH2:25][CH2:24][CH2:23][C:8]2[CH:9]=[C:10]3[C:19]4[CH:18]=[C:17](Br)[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:43])(=O)=O)=CC=1.O>C1COCC1>[C:1]([N:5]1[CH2:26][CH2:25][CH2:24][CH2:23][C:8]2[CH:9]=[C:10]3[C:19]4[CH:18]=[C:17]([F:43])[C:16]([O:21][CH3:22])=[CH:15][C:14]=4[CH2:13][CH2:12][N:11]3[C:7]=2[C:6]1=[O:27])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 962WaterHCID 588007N-FluorobenzenesulfonimideHCID 58124845HCID 58124845, compoundHCID 178418339Butyllithium

Product 1

HCID 581248809-tert-butyl-2-fluoro-3-methoxy-5,6,10,11,12,13-hexahydroazocino[4',3':4,5]pyrrolo[2,1-a]isoquinolin-8(9H)-oneYield 49.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a cooled (−60° C.) solution of 800 mg 19d in 10 mL THF was added 2.04 mmol n-butyllithium. After stirring at −60° C. for 30 min 877 mg N-fluorobenzenesulfonimide was added. The mixture was allowed to reach room temperature and was stirred for another 2 h. Water was added and the mixture was extracted with 2×ethyl acetate. The combined organic phases were dried and concentrated. The crude product by column chromatography over silica to afford an oil, which was crystallized from heptane/diisopropyl ethyl ether to give compound 340 mg of 27a as a pale yellow solid.

Workup

  1. additionwas added
  2. customto reach room temperature
  3. extractionthe mixture was extracted with 2×ethyl acetate
  4. customThe combined organic phases were dried
  5. concentrationconcentrated
  6. customThe crude product by column chromatography over silica to afford an oil, which
  7. customwas crystallized from heptane/diisopropyl ethyl ether

Sources & evidence

ORD record
ord-18106737d4e5441e84297cb965f8a9f8
Source dataset
uspto-grants-2013_04
Patent number
US08431564B2

Reaction notes

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