4-Toluenesulfonyl chloride → (R)-3-[(1R,3aR,4S,7aR)-4(tert-Butyl-dimethylsilanyloxy)-7a-methyl-octahydro-inden-1-yl]-butan-1-al

HRID 1604830

Reaktionsgleichung

Reaktionsgleichung von HRID 1604830
[Si:1]([O:8][C@H:9]1[CH2:17][CH2:16][CH2:15][C@@:14]2([CH3:18])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[C@H:19]([CH3:22])CO)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].S(Cl)(C1C=CC(C)=CC=1)(=O)=[O:24].CC1C=CN=C(N)[C:36]=1[CH3:42].[C-]#N.[Na+]>ClCCl.O>[Si:1]([O:8][C@H:9]1[CH2:17][CH2:16][CH2:15][C@@:14]2([CH3:18])[C@H:10]1[CH2:11][CH2:12][C@@H:13]2[C@H:19]([CH3:22])[CH2:42][CH:36]=[O:24])([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:2])[CH3:3]

Komponenten

7

Edukt 4

HCID 73974-Toluenesulfonyl chlorideHCID 8929Sodium CyanideHCID 110078842-Amino-3,4-dimethylpyridineHCID 15230899(S)-2-((1R,3aR,4S,7aR)-4-((tert-butyldimethylsilyl)oxy)-7a-methyloctahydro-1H-inden-1-yl)propan-1-ol

Produkt 1

HCID 18396012(R)-3-[(1R,3aR,4S,7aR)-4(tert-Butyl-dimethylsilanyloxy)-7a-methyl-octahydro-inden-1-yl]-butan-1-al

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
90 °C

Versuchsvorschrift

The compound (S)-2-[(1R,3aR,4S,7aR)-4-(tert-Butyl-dimethylsilanyloxy)-7a-methyl-octahydro-inden-1-yl]-propan-1-ol (5.00 g; 15.31 mmol) is dissolved in dichloromethane (75 ml) at room temperature. Tosyl chloride (8.76 g; 45.93 mmol; 3 equivalents) and dimethyl-aminopyridine (5.61 g; 45.93 mmol; 3 equivalents) are added. The mixture is allowed to react over night. The reaction mixture is poured on brine and extracted with ethyl-acetate. The organic phase is dried over sodium sulfate and the solvents are removed. The crude tosylate is directly used in the next step. The intermediate tosylate is dissolved in DMSO (35 ml), NaCN (2.25 g; 45.93 mmol; 3 equivalents) is added and heated for 2 hours at 90° C. The reaction mixture is poured in water and extracted with hexane/ethyl-acetate 1:1. The organic phase is dried over sodium sulfate and the solvents are removed. The crude cyanide is directly used in the next step. The intermediate cyanide is dissolved in dichloromethane (50 ml), DIBAH is added slowly at -10° C. (38.3 ml of a 1.2 M solution; 45.93 mmol; 3 equivalents) and stirred for 2 hours at -10° C. The temperature is allowed to raise above the freezing point and a 1 M aqueous solution of ammonium chloride is added. After 10 minutes a 2:1 ether/1 N aqueous HCl (30 ml) is added and allowed to react for 15 minutes. The reaction mixture is extracted with ethyl-acetate. The organic phase is dried over sodium sulfate and the solvents are removed. After flash-chromatography (hexane/ethyl-acetate 95:5) (R)-3-[(1R,3aR,4S,7aR)-4(tert-Butyl-dimethylsilanyloxy)-7a-methyl-octahydro-inden-1-yl]-butan-1-al is obtained as a colorless waxy solid.

Aufarbeitung

  1. customto react over night
  2. additionThe reaction mixture is poured on brine
  3. extractionextracted with ethyl-acetate
  4. dry with materialThe organic phase is dried over sodium sulfate
  5. customthe solvents are removed
  6. dissolutionThe intermediate tosylate is dissolved in DMSO (35 ml)
  7. extractionextracted with hexane/ethyl-acetate 1:1
  8. dry with materialThe organic phase is dried over sodium sulfate
  9. customthe solvents are removed
  10. dissolutionThe intermediate cyanide is dissolved in dichloromethane (50 ml)
  11. additionDIBAH is added slowly at -10° C. (38.3 ml of a 1.2 M solution
  12. temperatureto raise above the freezing point
  13. additiona 1 M aqueous solution of ammonium chloride is added
  14. additionAfter 10 minutes a 2:1 ether/1 N aqueous HCl (30 ml) is added
  15. customto react for 15 minutes
  16. extractionThe reaction mixture is extracted with ethyl-acetate
  17. dry with materialThe organic phase is dried over sodium sulfate
  18. customthe solvents are removed

Quellen und Nachweise

ORD-Eintrag
ord-8234e9dd84424b80904a5851a158203b
Quelldatensatz
uspto-grants-1999_11
Patentnummer
US05994569

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