Diisopropylethylamine → alpha-(Cyclohexylthio)-alpha-(3,4-dimethoxyphenyl)-3,4-dihydro-7-hydroxy-6-methoxy-2(1H)-isoquinolineheptanenitrile

HRID 1078790Notes

Reaction equation

HRID 1078790 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([S:20][CH:21]1[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1)([C:10]1[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=1)[C:8]#[N:9].CC([Si](C)(C)[O:32][C:33]1[CH:42]=[C:41]2[C:36]([CH2:37][CH2:38][NH:39][CH2:40]2)=[CH:35][C:34]=1[O:43][CH3:44])(C)C.C(N(CC)C(C)C)(C)C>C(#N)C>[CH:21]1([S:20][C:7]([C:10]2[CH:15]=[CH:14][C:13]([O:16][CH3:17])=[C:12]([O:18][CH3:19])[CH:11]=2)([CH2:6][CH2:5][CH2:4][CH2:3][CH2:2][N:39]2[CH2:38][CH2:37][C:36]3[C:41](=[CH:42][C:33]([OH:32])=[C:34]([O:43][CH3:44])[CH:35]=3)[CH2:40]2)[C:8]#[N:9])[CH2:26][CH2:25][CH2:24][CH2:23][CH2:22]1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 152855547-[[(1,1-Dimethylethyl)dimethylsily]oxy]-1,2,3,4-tetrahydro-6-methoxyisoquinolineHCID 19042070alpha-(5-Bromopentyl)-alpha-(cyclohexylthio)-3,4-dimethoxybenzeneacetonitrile

Product 1

HCID 10650088alpha-(Cyclohexylthio)-alpha-(3,4-dimethoxyphenyl)-3,4-dihydro-7-hydroxy-6-methoxy-2(1H)-isoquinolineheptanenitrileYield 150.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A mixture, under argon, of 2.17 g of product from Example 113, 1.8 g of product from Example 28, 13.0 ml of N,N-diisopropyl ethylamine and 80 ml of acetonitrile is heated under reflux temperature for 8 hours. The reaction is cooled and concentrated in vacuo and dried under high vacuum for 1 hour. The crude residue is dissolved in 70 ml of tetrahydrofuran and 10.0 ml of 1M tetrabutyl ammonium fluoride in tetrahydrofuran is added and the mixture is stirred at room temperature, under argon, for 2.5 hours. The mixture is poured into water and extracted with ethyl acetate. The organic layer is washed with saturated sodium chloride, dried, filtered, and concentrated in vacuo to give 4.0 g of a brown oil. The oil is purified by chromatography (silica gel: 1%, 1.5% and 2% methyl alcohol/methylene chloride)to give 2.1 g of the desired product.

Workup

  1. temperatureunder reflux temperature for 8 hours
  2. temperatureThe reaction is cooled
  3. concentrationconcentrated in vacuo
  4. customdried under high vacuum for 1 hour
  5. dissolutionThe crude residue is dissolved in 70 ml of tetrahydrofuran
  6. addition10.0 ml of 1M tetrabutyl ammonium fluoride in tetrahydrofuran is added
  7. additionThe mixture is poured into water
  8. extractionextracted with ethyl acetate
  9. washThe organic layer is washed with saturated sodium chloride
  10. customdried
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-155dd66a84b64974a607c71bb43624ef
Source dataset
uspto-grants-1996_08
Patent number
US05550149

Reaction notes

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