Iodine → (S)-((S)-5-(tert-butyldimethylsilyloxy)-2-cyclopentyl-4-iodo-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol

HRID 573743Notes

Reaction equation

HRID 573743 reaction equation
[Mg].II.Br[C:5]1[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=1.[Si:15]([O:22][C@H:23]1[CH2:32][C:31]([CH3:34])([CH3:33])[CH2:30][C:29]2[N:28]=[C:27]([CH:35]3[CH2:39][CH2:38][CH2:37][CH2:36]3)[C:26]([CH:40]=[O:41])=[C:25]([I:42])[C:24]1=2)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]>O1CCCC1>[Si:15]([O:22][C@H:23]1[CH2:32][C:31]([CH3:34])([CH3:33])[CH2:30][C:29]2[N:28]=[C:27]([CH:35]3[CH2:36][CH2:37][CH2:38][CH2:39]3)[C:26]([C@H:40]([C:5]3[CH:10]=[CH:9][C:8]([C:11]([F:14])([F:13])[F:12])=[CH:7][CH:6]=3)[OH:41])=[C:25]([I:42])[C:24]1=2)([C:18]([CH3:19])([CH3:20])[CH3:21])([CH3:17])[CH3:16]

Participants

6

Reactant 4

HCID 807IodineHCID 67872Benzene, 1-bromo-4-(trifluoromethyl)-2×HCID 5462224MagnesiumHCID 86662525HCID 86662525, compound

Product 1

HCID 66761287(S)-((S)-5-(tert-butyldimethylsilyloxy)-2-cyclopentyl-4-iodo-7,7-dimethyl-5,6,7,8-tetrahydroquinolin-3-yl)(4-(trifluoromethyl)phenyl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-50 °C

Procedure

To 300 mg magnesium turnings and 2 crystals of iodine were added 1 ml tetrahydrofurane. Afterwards a few drops of a solution of 2 ml 4-bromobenzotrifluoride in 15 ml tetrahydrofurane were added and the mixture was gently heated to start the reaction. Then the rest of the 4-bromobenzotrifluoride solution is added dropwise. After complete formation the Grignard reagent is added dropwise via syringe to a solution of 880 mg (S)-5-(tert-butyldimethylsilyloxy)-2-cyclopentyl-4-iodo-7,7-dimethyl-5,6,7,8-tetrahydroquinoline-3-carbaldehyde in 10 ml tetrahydrofurane at −50° C. The reaction is stirred for 1 hour at −50° C. and then quenched by dropwise addition of 10 ml methanol. The mixture is partitioned between dichloromethane and saturated ammonium chloride. The organic phase is washed with brine and dried with sodium sulphate. The solvents are evaporated in vacuo and the residue is chromatographed on silica gel (cyclohexane/ethylacetate 100:0 to 95:5).

Workup

  1. temperaturethe mixture was gently heated
  2. customthe reaction
  3. customquenched by dropwise addition of 10 ml methanol
  4. customThe mixture is partitioned between dichloromethane and saturated ammonium chloride
  5. washThe organic phase is washed with brine
  6. dry with materialdried with sodium sulphate
  7. customThe solvents are evaporated in vacuo
  8. customthe residue is chromatographed on silica gel (cyclohexane/ethylacetate 100:0 to 95:5)

Sources & evidence

ORD record
ord-86a95939cbb84265bab44bbd4b83d381
Source dataset
uspto-grants-2015_05
Patent number
US09029544B2

Reaction notes

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