Cesium carbonate → 1-(2-(Trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidine

HRID 1254199

Reaction equation

HRID 1254199 reaction equation
[CH:1]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)=[CH2:2].C([O-])([O-])=O.[Cs+].[Cs+].[CH3:15][Si:16]([CH3:43])([CH3:42])[CH2:17][CH2:18][S:19]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([CH:28]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2Br)[CH2:23]1)(=[O:21])=[O:20]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[CH3:15][Si:16]([CH3:43])([CH3:42])[CH2:17][CH2:18][S:19]([N:22]1[CH2:27][CH2:26][CH2:25][CH:24]([CH:28]([O:36][CH2:37][CH2:38][CH2:39][O:40][CH3:41])[C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][C:30]=2[CH2:2][CH2:1][CH:3]2[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]2)[CH2:23]1)(=[O:21])=[O:20]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 12757VinylcyclohexaneHCID 59382843HCID 59382843, compound

Product 1

HCID 593829951-(2-(Trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidineYield 82%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

A sealed tube designed for a microwave reactor was filled with nitrogen and charged with vinylcyclohexane (66 mg, 0.595 mmol, 5.0 equiv) 9-BBN (0.5 M solution in THF, 1.07 mL, 4.5 equiv) and the clear solution was stirred overnight at rt. The flask was briefly opened and Cs2CO3 (213 mg, 0.119 mmol, 3.3 equiv), PdCl2(dppf) (11 mg, 0.119 mmol, 0.05 equiv), 1-(2-(trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-bromophenyl)methyl)-piperidine (100 mg, 0.197 mmol, 1.0 equiv), and dioxane (4 mL) added. The tube was degassed by three evacuate/N2 backfill cycles, then placed in a CEM microwave reactor and heated to 120° C. for 10 min. The solvent was removed and the product was extracted with EtOAc and filtered through a pad of Celite. The product was purified by flash chromatography on 12 g of silica, eluting with 0 to 27% EtOAc in hexanes, to afford 1-(2-(trimethylsilyl)ethanesulfonyl)-3-((3-methoxypropoxy)(2-(2-cyclohexylethyl)phenyl)methyl)piperidine (82%) as a mixture of diastereomers. 1H NMR (CDCl3) δ 0.02 (s, 9H), 0.8-1.9 (m, 24H), 2.5-2.8 (m, 4H), 3.3-4.4 (m, 11H), 7.1-7.3 (m, 4H). MS ESI +ve m/z 561 (M+Na+).

Workup

  1. customA sealed tube designed for a microwave reactor
  2. additionwas filled with nitrogen
  3. customThe tube was degassed by three
  4. customevacuate/N2 backfill cycles
  5. temperatureheated to 120° C. for 10 min
  6. customThe solvent was removed
  7. extractionthe product was extracted with EtOAc
  8. filtrationfiltered through a pad of Celite
  9. customThe product was purified by flash chromatography on 12 g of silica
  10. washeluting with 0 to 27% EtOAc in hexanes

Sources & evidence

ORD record
ord-6a880111eb96489c85fcc14ca3da3b74
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Linked notes

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