HCID 68000325, compound → HCID 67999636, compound

HRID 932084Notes

Reaction equation

HRID 932084 reaction equation
[CH2:1]([C@@:4]1([CH3:33])[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][CH:18]=2)[N:6]([C@H:24]([CH2:27][CH2:28][C:29](=[O:31])[CH3:30])[CH2:25][CH3:26])[C:5]1=[O:32])[CH:2]=[CH2:3].[CH3:34][Mg]Br>C1COCC1.C1(C)C=CC=CC=1>[CH2:1]([C@@:4]1([CH3:33])[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:18]=[CH:19][C:20]([Cl:23])=[CH:21][CH:22]=2)[N:6]([C@H:24]([CH2:27][CH2:28][C:29]([OH:31])([CH3:34])[CH3:30])[CH2:25][CH3:26])[C:5]1=[O:32])[CH:2]=[CH2:3]

Participants

5

Reactant 2

HCID 68000325HCID 68000325, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 67999636HCID 67999636, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (3S,5R,6S)-3-allyl-5-(3-chlorophenyl)-6-(4-chlorophenyl)-3-methyl-1-((S)-6-oxoheptan-3-yl)piperidin-2-one prepared above in Step C (78 mg, 0.16 mmol) in THF (1.6 mL) was added 1.4 M methylmagnesium bromide in toluene and THF (75:25) (344 μL, 0.481 mmol) at 0° C. Then the reaction was allowed to warm to rt and stirred for 2 h. The reaction was quenched (sat NH4Cl solution), extracted (2×EtOAc), and washed (sat. aq. NaCl solution). The combined organic layer was dried (Na2SO4) and concentrated under reduced pressure. Purification of the residue by chromatography on silica gel (12 g SiO2, 33% and 43% EtOAc/Hex) provided the title compound as a colorless foam.

Workup

  1. customThe reaction was quenched (sat NH4Cl solution)
  2. extractionextracted (2×EtOAc)
  3. washwashed (sat. aq. NaCl solution)
  4. dry with materialThe combined organic layer was dried (Na2SO4)
  5. concentrationconcentrated under reduced pressure
  6. customPurification of the residue by chromatography on silica gel (12 g SiO2, 33% and 43% EtOAc/Hex)

Sources & evidence

ORD record
ord-fc61658794d346dd97964d2ae59f15fd
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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