Sodium hydride → Sdz pco 400

HRID 1460613Notes

Reaction equation

HRID 1460613 reaction equation
[CH2:1]1[C:6](=[O:7])[CH2:5][C:3](=[O:4])[CH2:2]1.[H-].[Na+].[O:10]1[CH:16]2[CH:11]1[C:12]([CH3:24])([CH3:23])[O:13][C:14]1[CH:20]=[CH:19][C:18]([C:21]#[N:22])=[CH:17][C:15]=12>O1CCCC1.[Cu]Br>[OH:10][C@H:11]1[C@H:16]([O:4][C:3]2[CH2:2][CH2:1][C:6](=[O:7])[CH:5]=2)[C:15]2[CH:17]=[C:18]([C:21]#[N:22])[CH:19]=[CH:20][C:14]=2[O:13][C:12]1([CH3:24])[CH3:23]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 774661,3-CyclopentanedioneHCID 108673602,2-Dimethyl-3,4-epoxy-6-cyanochroman

Product 1

HCID 129348Sdz pco 400

Reagents, catalysts & solvents 2

HCID 24593copper(I) bromideCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

10.1 g of 1,3-cyclopentadione are dissolved in 1000 ml of tetrahydrofuran under a protective gas, and 2.7 g of sodium hydride (80%) are slowly added. After half an hour, 18.5 g copper(I)bromide.dimethylsulphide complex were added to this mixture. To this reaction solution are added in drops 12.1 g of 3,4-epoxy-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-6-carbonitrile (J. M. Evans et al., J. Med. Chem. 26, 1582 [1983]) in 100 ml of tetrahydrofuran. After 67 hours, the reaction is quenched with water, and the reaction solution is subsequently partitioned between dichloromethane and water. Drying of the organic phase over sodium sulphate, filtration and concentration on a rotary evaporator yields a yellowish mass, which is purified by flash-chromatography (dichlormethane, 1% methanol). Recrystallisation from dichloromethane/ethanol yields white crystals having a m.p. of 199°-201° C.

Workup

  1. additionare slowly added
  2. waitAfter half an hour
  3. additiondimethylsulphide complex were added to this mixture
  4. customthe reaction is quenched with water
  5. customthe reaction solution is subsequently partitioned between dichloromethane and water
  6. dry with materialDrying of the organic phase over sodium sulphate, filtration and concentration on a rotary evaporator
  7. customyields a yellowish mass, which
  8. customis purified by flash-chromatography (dichlormethane, 1% methanol)
  9. customRecrystallisation from dichloromethane/ethanol
  10. customyields white crystals

Sources & evidence

ORD record
ord-537a48821d6c496ba2072cff188dd360
Source dataset
uspto-grants-1991_12
Patent number
US05071871

Reaction notes

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