Benzene, 1-iodo-4-(trifluoromethyl)- → (9S)-9-(tert-Butyldimethylsilyloxy)-4-isopropyl-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

HRID 573802Notes

Reaction equation

HRID 573802 reaction equation
I[C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=1.C([Li])(C)(C)C.[Si:17]([O:24][C@H:25]1[CH2:34][C:33]([CH3:36])([CH3:35])[CH2:32][C:31]2[N:30]=[C:29]([CH:37]([CH3:39])[CH3:38])[C:28]3[C:40](=[O:48])[O:41][C:42]4([CH2:47][CH2:46][O:45][CH2:44][CH2:43]4)[C:27]=3[C:26]1=2)([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18]>O1CCCC1.CCCCC>[Si:17]([O:24][C@H:25]1[CH2:34][C:33]([CH3:35])([CH3:36])[CH2:32][C:31]2[N:30]=[C:29]([CH:37]([CH3:38])[CH3:39])[C:28]3[C:40]([C:2]4[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][CH:3]=4)([OH:48])[O:41][C:42]4([CH2:43][CH2:44][O:45][CH2:46][CH2:47]4)[C:27]=3[C:26]1=2)([C:20]([CH3:22])([CH3:23])[CH3:21])([CH3:18])[CH3:19]

Participants

6

Reactant 3

HCID 67993Benzene, 1-iodo-4-(trifluoromethyl)-HCID 66762310(S)-9-(tert-Butyldimethylsilyloxy)-4-isopropyl-7,7-dimethyl-2',3',5',6,6',7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4'-pyran]-3-oneHCID 178418306HCID 178418306, compound

Product 1

HCID 66762580(9S)-9-(tert-Butyldimethylsilyloxy)-4-isopropyl-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

Reagents, catalysts & solvents 2

HCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

0.12 g 1-Iodo-4-(trifluoromethyl)benzene are dissolved in 3 ml tetrahydrofurane, cooled to −78° C. and treated dropwise with 0.54 ml of a 1.6 M solution of tert.-butyllithium in n-pentan. The mixture is stirred for 30 minutes and then a solution of 0.10 g (S)-9-(tert-butyldimethylsilyloxy)-4-isopropyl-7,7-dimethyl-2′,3′,5′,6,6′,7,8,9-octahydro-3H-spiro[furo[3,4-c]quinoline-1,4′-pyran]-3-one in 1 ml tetrahydrofurane is added dropwise. The mixture is stirred for 30 minutes at −78° C. and for 1 hour at −40° C. Then the reaction is quenched by addition of 0.5 ml methanol and purified via reversed phase chromatography (Varian Pursiut XRs C18 10μ, water/methanol/trifluoroacetic acid 90:10:0.1 to 0:100:0.1; 180 mL/min; 18 min).

Workup

  1. stirringThe mixture is stirred for 30 minutes at −78° C. and for 1 hour at −40° C
  2. customThen the reaction is quenched by addition of 0.5 ml methanol
  3. custompurified
  4. customphase chromatography (Varian Pursiut XRs C18 10μ, water/methanol/trifluoroacetic acid 90:10:0.1 to 0:100:0.1; 180 mL/min; 18 min)

Sources & evidence

ORD record
ord-e0e67c16a88a4aba856660d5926ad5d3
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Reaction notes

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