Triethylsilane → (3S,9S)-9-(tert-Butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-3-(4-(trifluoromethyl)phenyl)-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]

HRID 573788Notes

Reaction equation

HRID 573788 reaction equation
[Si:1]([O:8][C@H:9]1[CH2:18][C:17]([CH3:20])([CH3:19])[CH2:16][C:15]2[N:14]=[C:13]([Cl:21])[C:12]3[C:22]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=4)(O)[O:23][C:24]4([CH2:29][CH2:28][O:27][CH2:26][CH2:25]4)[C:11]=3[C:10]1=2)([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].C([SiH](CC)CC)C>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[Si:1]([O:8][C@H:9]1[CH2:18][C:17]([CH3:20])([CH3:19])[CH2:16][C:15]2[N:14]=[C:13]([Cl:21])[C:12]3[C@H:22]([C:31]4[CH:36]=[CH:35][C:34]([C:37]([F:40])([F:39])[F:38])=[CH:33][CH:32]=4)[O:23][C:24]4([CH2:25][CH2:26][O:27][CH2:28][CH2:29]4)[C:11]=3[C:10]1=2)([C:4]([CH3:5])([CH3:6])[CH3:7])([CH3:3])[CH3:2]

Participants

5

Reactant 2

HCID 12052TriethylsilaneHCID 86662530(9S)-9-(tert-butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-3-(4-(trifluoromethyl)phenyl)-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-ol

Product 1

HCID 86662529(3S,9S)-9-(tert-Butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-3-(4-(trifluoromethyl)phenyl)-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-50 °C

Procedure

1.32 g (9S)-9-(tert-butyldimethylsilyloxy)-4-chloro-7,7-dimethyl-3-(4-(trifluoromethyl)phenyl)-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-3-ol and 2.9 ml triethylsilane are dissolved in 40 ml dichloromethane, cooled to −50° C. and treated dropwise with 4.4 ml of a 1 m solution of titanium-(IV)-chloride in dichloromethane. Then the mixture is allowed to warm to room temperature and stirred for 30 minutes. The mixture is partitioned between saturated solution of sodium bicarbonate in water and dichloromethane. The aqueous phase is twice extracted with dichloromethane. The combined organic phases are dried with sodium sulphate and the solvents are evaporated in vacuo. The residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 90:10).

Workup

  1. temperatureto warm to room temperature
  2. customThe mixture is partitioned between saturated solution of sodium bicarbonate in water and dichloromethane
  3. extractionThe aqueous phase is twice extracted with dichloromethane
  4. dry with materialThe combined organic phases are dried with sodium sulphate
  5. customthe solvents are evaporated in vacuo
  6. customThe residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 90:10)

Sources & evidence

ORD record
ord-e0a21f984aaa4bc28b9a10af051ec652
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Reaction notes

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