Sodium hydride → HCID 67998728, compound

HRID 932058Notes

Reaction equation

HRID 932058 reaction equation
[CH2:1]([C@@:4]1([CH3:25])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)[NH:6][C:5]1=[O:24])[CH:2]=[CH2:3].[H-].[Na+].Br[CH:29]([CH2:37][CH3:38])[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31]>CN(C=O)C>[CH2:1]([C@@:4]1([CH3:25])[CH2:9][C@H:8]([C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([Cl:16])[CH:11]=2)[C@@H:7]([C:17]2[CH:22]=[CH:21][C:20]([Cl:23])=[CH:19][N:18]=2)[N:6]([CH:29]([CH2:37][CH3:38])[C:30]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])=[O:31])[C:5]1=[O:24])[CH:2]=[CH2:3]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 13124118tert-Butyl 2-bromobutanoateHCID 68000991HCID 68000991, compound

Product 1

HCID 67998728HCID 67998728, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-3-methylpiperidin-2-one (77 mg, 0.205 mmol, Example 124, Step C) in DMF (0.3 mL) was added slowly 9.5 mg (0.24 mmol) of a dispersion of 60% sodium hydride in mineral oil followed by tert-butyl 2-bromobutanoate (92 mg, 0.410 mmol). The reaction was stirred at ambient temperature overnight, quenched with MeOH/HOAc, was diluted with EtOAc and water and extracted to EtOAc. The organics were dried over Na2SO4, filtered and the filtrate was concentrated. Purification by reversed phase preparatory HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.) (eluent: 70% acetonitrile, water, 0.1% TFA) provided the title compound, as well as its stereoisomer, (R)-tert-butyl 2-((3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(5-chloropyridin-2-yl)-3-methyl-2-oxopiperidin-1-yl)butanoate.

Workup

  1. customquenched with MeOH/HOAc
  2. additionwas diluted with EtOAc and water
  3. extractionextracted to EtOAc
  4. dry with materialThe organics were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customPurification by reversed phase preparatory HPLC (Sunfire™ Prep C18 OBD 10 μm column (Waters, Milford, Mass.) (eluent: 70% acetonitrile, water, 0.1% TFA)

Sources & evidence

ORD record
ord-44e62fa1592e44cc88f3adbae69aa8ac
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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