Methyl iodide → (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

HRID 1048267Notes

Reaction equation

HRID 1048267 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:11](=[O:30])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.IC.[CH3:33][Si]([N-][Si](C)(C)C)(C)C.[Li+]>C1COCC1>[Cl:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:13]([C:14]3[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=3)[N:12]([C@@H:21]([CH2:28][CH3:29])[CH2:22][O:23][CH2:24][CH:25]3[CH2:27][CH2:26]3)[C:11](=[O:30])[CH:10]([CH3:33])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 2733832Lithium HexamethyldisilazideHCID 58573287(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one

Product 1

HCID 67999671(5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)-3-methylpiperidin-2-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 0.325 g (0.73 mmol) of (5R,6S)-5-(3-chlorophenyl)-6-(4-chlorophenyl)-1-((S)-1-(cyclopropylmethoxy)butan-2-yl)piperidin-2-one (Example 68, Step B) and iodomethane (0.055 mL, 0.874 mmol) in THF (7.0 mL) was added lithium bis(trimethylsilyl)amide (1M solution in THF, 0.8 mL, 0.8 mmol) at −78° C. The reaction was allowed to warm to R.T., then was quenched with sat. aqueous NH4Cl solution and extracted with EtOAc. The combined organic layers were washed with water and sat. aq. NaCl solution, dried over MgSO4, filtered and the filtrate was concentrated under reduced pressure.

Workup

  1. customwas quenched with sat. aqueous NH4Cl solution
  2. extractionextracted with EtOAc
  3. washThe combined organic layers were washed with water and sat. aq. NaCl solution
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-59f2b9012646494789d9938d39f583e8
Source dataset
uspto-grants-2013_10
Patent number
US08569341B2

Reaction notes

Loading…