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

HRID 573786Notes

Reaction equation

HRID 573786 reaction equation
[CH2:1]([Zn]CC)C.FC(F)(F)C(O)=O.ICI.[Si:16]([O:23][C@H:24]1[CH2:33][C:32]([CH3:35])([CH3:34])[CH2:31][C:30]2[N:29]=[C:28]([C:36]([CH3:38])=[CH2:37])[C:27]3[C@@H:39]([C:47]4[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:55])[F:54])=[CH:49][CH:48]=4)[O:40][C:41]4([CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:26]=3[C:25]1=2)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]>ClCCl>[Si:16]([O:23][C@H:24]1[CH2:33][C:32]([CH3:35])([CH3:34])[CH2:31][C:30]2[N:29]=[C:28]([C:36]3([CH3:1])[CH2:38][CH2:37]3)[C:27]3[C@@H:39]([C:47]4[CH:52]=[CH:51][C:50]([C:53]([F:56])([F:54])[F:55])=[CH:49][CH:48]=4)[O:40][C:41]4([CH2:46][CH2:45][O:44][CH2:43][CH2:42]4)[C:26]=3[C:25]1=2)([C:19]([CH3:20])([CH3:21])[CH3:22])([CH3:18])[CH3:17]

Participants

6

Reactant 4

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 66762113(3R,9S)-9-(tert-butyldimethylsilyloxy)-7,7-dimethyl-4-(prop-1-en-2-yl)-3-(4-(trifluoromethyl)phenyl)-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]HCID 178418750HCID 178418750, compound

Product 1

HCID 66761645(3R,9S)-9-(tert-butyldimethylsilyloxy)-7,7-dimethyl-4-(1-methylcyclopropyl)-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 1

HCID 6344DichloromethaneSolvent4×

Conditions

Temperature
0 °C

Procedure

536 μl Diethylzinc (1 M in n-hexane) are dissolved in 5 ml dichloromethane, cooled to 0° C. and treated dropwise with a solution of 41 μl trifluoroacetic acid in 5 ml dichloromethane. The mixture is stirred for 20 minutes and then 41 μl diiodomethane in 2.5 ml dichloromethane are added dropwise. After stirring for further 20 minutes a solution of 150 mg (3R,9S)-9-(tert-butyldimethylsilyloxy)-7,7-dimethyl-4-(prop-1-en-2-yl)-3-(4-(trifluoromethyl)phenyl)-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran] in 2.5 ml dichloromethane are added dropwise. The mixture is then allowed to warm to room temperature and is stirred for 4 hours. Then it 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 85:15).

Workup

  1. additionare added dropwise
  2. temperatureto warm to room temperature
  3. stirringis stirred for 4 hours
  4. customThen it is partitioned between saturated solution of sodium bicarbonate in water and dichloromethane
  5. extractionThe aqueous phase is twice extracted with dichloromethane
  6. dry with materialThe combined organic phases are dried with sodium sulphate
  7. customthe solvents are evaporated in vacuo
  8. customThe residue is chromatographed on silica gel (petrole ether/ethylacetate 100:0 to 85:15)

Sources & evidence

ORD record
ord-8bfa8cfc1fc74ff58ee0f8e392218a25
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Reaction notes

Loading…