Chlorotrimethylsilane → (R)-4-dimethylamino-1-(2-methyl-5-(triethylsilyl)pent-4-inyl)-4-phenylcyclohexanol

HRID 2064535Notes

Reaction equation

HRID 2064535 reaction equation
C([Li])(C)(C)C.[CH2:6]([Si:8]([CH2:18][CH3:19])([CH2:16][CH3:17])[C:9]#[C:10][CH2:11][C@@H:12]([CH3:15])[CH2:13]I)[CH3:7].[CH3:20][N:21]([CH3:35])[C:22]([C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)([CH2:27][CH3:28])[CH2:23][C:24](=O)[CH3:25].C[Si](C)(C)Cl.[Cl-].[NH4+].C(=O)([O-])[OH:44].[Na+]>CCCCC.C(OCC)C>[CH3:20][N:21]([CH3:35])[C:22]1([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)[CH2:27][CH2:28][C:25]([CH2:13][C@H:12]([CH3:15])[CH2:11][C:10]#[C:9][Si:8]([CH2:18][CH3:19])([CH2:16][CH3:17])[CH2:6][CH3:7])([OH:44])[CH2:24][CH2:23]1

Participants

9

Reactant 6

HCID 6397ChlorotrimethylsilaneHCID 25517Ammonium ChlorideHCID 516892Sodium BicarbonateHCID 686327414-Dimethylamino-4-phenylhexanoneHCID 131729995triethyl-((R)-5-iodo-4-methylpent-1-inyl)silaneHCID 178418306HCID 178418306, compound

Product 1

HCID 131729994(R)-4-dimethylamino-1-(2-methyl-5-(triethylsilyl)pent-4-inyl)-4-phenylcyclohexanol

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8003PentaneSolvent

Procedure

A 1.7 M solution of tert-butyl lithium (7.8 mL, 13.3 mmol) in pentane was added in drops to a solution of triethyl-((R)-5-iodo-4-methylpent-1-inyl)silane (2.15 g, 6.6 mmol) in anhydrous diethyl ether (100 mL) at −85° C. in argon, wherein the inside temperature was held at −85° C. After stirring for 2 h at −85° C. a solution of 4-dimethylamino-4-phenylhexanone (1.43 g, 6.6 mmol) in anhydrous diethyl ether (30 mL) was added in drops at this temperature and stirred for a further 30 min. A solution of trimethylchlorosilane (1.44 g, 1.69 mL, 13.3 mmol) in diethyl ether (12 mL) was then added to the solution in drops and slowly heated to room temperature. The reaction mixture was then mixed with saturated ammonium chloride solution (20 mL) and the separated solid (2.00 g) was filtered off. The phases were separated and the aqueous [phase?] extracted with diethyl ether (3×30 mL). The combined diethyl ether phases were washed with sodium chloride solution (20 mL), dried with sodium sulphate, filtered and concentrated to low volume in a vacuum. No target product could be isolated from this phase. The separated solid (2.00 g) was then mixed with saturated sodium hydrogencarbonate solution (50 mL) and the resulting suspension extracted with ethyl acetate (3×30 mL). The combined ethyl acetate phases were dried with sodium sulphate and concentrate to low volume in a vacuum. The raw product (351 mg) was purified by flash chromatography (18 g, 20×2.0 cm) with ethyl acetate/cyclohexane (1:2).

Workup

  1. customwas held at −85° C
  2. additionwas added in drops at this temperature
  3. filtrationthe separated solid (2.00 g) was filtered off
  4. customThe phases were separated
  5. extractionthe aqueous [phase?] extracted with diethyl ether (3×30 mL)
  6. washThe combined diethyl ether phases were washed with sodium chloride solution (20 mL)
  7. dry with materialdried with sodium sulphate
  8. filtrationfiltered
  9. concentrationconcentrated to low volume in a vacuum
  10. customNo target product could be isolated from this phase
  11. extractionthe resulting suspension extracted with ethyl acetate (3×30 mL)
  12. dry with materialThe combined ethyl acetate phases were dried with sodium sulphate
  13. concentrationconcentrate to low volume in a vacuum
  14. customThe raw product (351 mg) was purified by flash chromatography (18 g, 20×2.0 cm) with ethyl acetate/cyclohexane (1:2)

Sources & evidence

ORD record
ord-1f0a1e60d2044b8aa048ddd9ffbc1e22
Source dataset
uspto-grants-2012_10
Patent number
US08288430B2

Reaction notes

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