Citric Acid → HCID 68000146, compound

HRID 931908Notes

Reaction equation

HRID 931908 reaction equation
[CH2:1]([C@H:4]1[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][CH3:28])[CH2:25][NH2:26])[C:5]1=[O:29])[CH:2]=[CH2:3].[CH3:30][S:31](Cl)(=[O:33])=[O:32].N1C=CC=CC=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(Cl)Cl>[CH2:1]([C@H:4]1[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][CH3:28])[CH2:25][NH:26][S:31]([CH3:30])(=[O:33])=[O:32])[C:5]1=[O:29])[CH:2]=[CH2:3]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 67998459HCID 67998459, compound

Product 1

HCID 68000146HCID 68000146, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 69 mg (0.16 mmol) of (3S,5R,6S)-3-allyl-1-((S)-1-aminobutan-2-yl)-5-(3-chlorophenyl)-6-(4-chlorophenyl)piperidin-2-one (Example 28, Step B from the non-racemic precursor described in Example 19, Step A) in 1.6 mL of DCM was added methanesulfonyl chloride (13.7 μL, 0.175 mmol) and pyridine (38.7 μL, 0.478 mmol) successively at 0° C. After being stirred at rt for 14 h the reaction mixture was acidified with 10% aq. citric acid and extracted (2×DCM). The combined organic layers were washed with sat. NaCl solution, dried over Na2SO4, filtered and the filtrate was concentrated under reduced pressure. Purification by reversed phase HPLC (40 to 90% MeCN/H2O in 45 min, 2 injections, tR=25.94 min) provided the title compound as a yellow solid.

Workup

  1. extractionextracted (2×DCM)
  2. washThe combined organic layers were washed with sat. NaCl solution
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. customPurification by reversed phase HPLC (40 to 90% MeCN/H2O in 45 min, 2 injections, tR=25.94 min)

Sources & evidence

ORD record
ord-18d6e635d9a549c2836d4a506660bf8d
Source dataset
uspto-grants-2016_03
Patent number
US09296736B2

Reaction notes

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