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

HRID 1692101Notes

Reaction equation

HRID 1692101 reaction equation
O.C(O)(C(F)(F)F)=O.[Cl:9][C:10]1[CH:11]=[C:12]([C:41]2[CH:46]=[CH:45][C:44]([C:47]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:48])=[CH:43][CH:42]=2)[CH:13]=[C:14]([Cl:40])[C:15]=1[CH2:16][C@@H:17]1[CH2:21][CH2:20][N:19]([N:22]2[CH2:27][CH2:26][CH:25]([O:28][Si](C(C)C)(C(C)C)C(C)C)[CH2:24][CH2:23]2)[C:18]1=[O:39]>C1COCC1>[Cl:40][C:14]1[CH:13]=[C:12]([C:41]2[CH:42]=[CH:43][C:44]([C:47]([N:49]3[CH2:54][CH2:53][O:52][CH2:51][CH2:50]3)=[O:48])=[CH:45][CH:46]=2)[CH:11]=[C:10]([Cl:9])[C:15]=1[CH2:16][C@@H:17]1[CH2:21][CH2:20][N:19]([N:22]2[CH2:27][CH2:26][CH:25]([OH:28])[CH2:24][CH2:23]2)[C:18]1=[O:39]

Participants

5

Reactant 3

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 66905099(R)-3-[3,5-Dichloro-4'-(morpholine-4-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

Product 1

HCID 57672062(R)-3-[3,5-Dichloro-4'-(morpholine-4-carbonyl)-biphenyl-4-ylmethyl]-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-oneYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Add water (3 mL) and TFA (1 mL) to a solution of (R)-3-[3,5-Dichloro-4′-(morpholine-4-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one in THF (3 mL). Stir the mixture at room temp for 12 hours. Partition the reaction with ethyl acetate (20 mL) and sodium bicarbonate (sat. solution, 15 mL), separate the organic layer, extract the aqueous with another 20 mL of ethyl acetate, and combine the organic solutions. Dry over sodium sulfate, filter and concentrate. Dissolve the residue in 4 mL of dichloromethane, load on silica gel column, and flash with ethyl acetate for 15 minutes and then switch to 8% methanol in dichloromethane to afford 0.13 grams (84%) of the desired product as white solid. MS (m/z): 532 (M+).

Workup

  1. customPartition
  2. customthe reaction with ethyl acetate (20 mL) and sodium bicarbonate (sat. solution, 15 mL)
  3. customseparate the organic layer
  4. extractionextract the aqueous with another 20 mL of ethyl acetate
  5. dry with materialDry over sodium sulfate
  6. filtrationfilter
  7. concentrationconcentrate
  8. dissolutionDissolve the residue in 4 mL of dichloromethane
  9. waitload on silica gel column, and flash with ethyl acetate for 15 minutes

Sources & evidence

ORD record
ord-ff5838a05b684171b6bfafd02d84d415
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

Loading…