Water → (R)-3-(3,5-Dichloro-4'-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-one

HRID 1692108Notes

Reaction equation

HRID 1692108 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:41])=[O:40])=[CH:35][CH:34]=2)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([O:20][Si](C(C)C)(C(C)C)C(C)C)[CH2:16][CH2:15]2)[C:10]1=[O:31].O.C(O)(C(F)(F)F)=O>C1COCC1.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:33]2[CH:38]=[CH:37][C:36]([S:39]([CH3:42])(=[O:40])=[O:41])=[CH:35][CH:34]=2)[CH:5]=[C:6]([Cl:32])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH2:12][N:11]([N:14]2[CH2:19][CH2:18][CH:17]([OH:20])[CH2:16][CH2:15]2)[C:10]1=[O:31]

Participants

6

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 66905070(R)-3-(3,5-Dichloro-4'-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

Product 1

HCID 57672048(R)-3-(3,5-Dichloro-4'-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-oneYield 96.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (R)-3-(3,5-Dichloro-4′-methanesulfonyl-biphenyl-4-ylmethyl)-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one (0.12 g) in THF (6 mL), add water (6 mL) and TFA (2 mL). Stir the mixture at room temperature for 12 hours. Dilute the reaction mixture with ethyl acetate and wash with sodium bicarbonate (Sat.) and water. Separate the organic and dry over sodium sulfate, filter and concentrate. Purify the crude mixture on silica gel column with 50% ethyl acetate in hexane to 100% ethyl acetate to afford 0.088 g of the titled product. MS (m/z): 497 (M+).

Workup

  1. washwash with sodium bicarbonate (Sat.) and water
  2. customSeparate the organic and
  3. dry with materialdry over sodium sulfate
  4. filtrationfilter
  5. concentrationconcentrate
  6. customPurify the crude mixture on silica gel column with 50% ethyl acetate in hexane to 100% ethyl acetate

Sources & evidence

ORD record
ord-b57e68bba6f4432b801d0f8741b43fd4
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

Loading…