Tetracyanoquinodimethane → HCID 58580848, compound

HRID 1920791Notes

Reaction equation

HRID 1920791 reaction equation
[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[CH2:12][C@@H:13]([OH:33])[CH2:14][O:15][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=2/[CH:26]=[CH:27]/[C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:17])=[CH:4][C:3]=1[F:36].C1C(=C(C#N)C#N)C=CC(=C(C#N)C#N)C=1.[BH4-].[Na+]>O.O.O.O.O.O.[Ni](Cl)Cl.O.C(O)C.O1CCCC1>[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][C@@H:7]2[CH2:11][CH2:10][CH2:9][N:8]2[CH2:12][C@@H:13]([OH:33])[CH2:14][O:15][C@@H:16]([C:18]2[CH:23]=[CH:22][CH:21]=[C:20]([O:24][CH3:25])[C:19]=2[CH2:26][CH2:27][C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH3:17])=[CH:4][C:3]=1[F:36]

Participants

8

Reactant 3

HCID 73697TetracyanoquinodimethaneHCID 4311764Sodium borohydrideHCID 58580958HCID 58580958, compound

Product 1

HCID 58580848HCID 58580848, compoundYield 49%

Reagents, catalysts & solvents 4

HCID 11791229Dichloronickel;hexahydrateCatalystHCID 702EthanolSolvent2×HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of ethyl (2E)-3-{2-[(1R)-1-({(2R)-3-[(2S)-2-(4-chloro-3-fluorobenzyl)pyrrolidin-1-yl]-2-hydroxypropyl}oxy)ethyl]-6-methoxy phenyl}prop-2-enoate (516 mg, 992.3 μmol), which had been obtained in Example 168 (168a), in mixture of tetrahydrofuran (10 mL) and ethanol (2 mL) was added with nickel (II) chloride hexahydrate (117.9 mg, 496.1 μmol) and 7,7,8,8-tetracyanoquinodimethane (101.3 mg, 496.1 μmol), and stirred for 5 minutes under ice cooling. After stirring, a solution of sodium borohydride (150 mg, 3.97 mmol) in mixture of tetrahydrofuran (5 mL) and ethanol (1 mL) was added dropwise slowly thereto under ice cooling. Upon the completion of the dropwise addition, the mixture was stirred for 1 hour at room temperature, added with water (20 mL), and filtered. The solvent was distilled off under reduced pressure. The residue was extracted with ethyl acetate (40 mL×2). After that, the organic layers were washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (n-hexane/ethyl acetate=1/2) to give the title compound as a colorless oily substance (253 mg, yield 49%).

Workup

  1. stirringAfter stirring
  2. additionwas added dropwise slowly
  3. additionUpon the completion of the dropwise addition
  4. stirringthe mixture was stirred for 1 hour at room temperature
  5. filtrationfiltered
  6. distillationThe solvent was distilled off under reduced pressure
  7. extractionThe residue was extracted with ethyl acetate (40 mL×2)
  8. washAfter that, the organic layers were washed with saturated brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. distillationThe solvent was distilled off under reduced pressure
  11. customThe residue was purified by silica gel chromatography (n-hexane/ethyl acetate=1/2)

Sources & evidence

ORD record
ord-76a656ec046e417a928456bcfc8243c0
Source dataset
uspto-grants-2012_05
Patent number
US08173631B2

Reaction notes

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