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

HRID 1692099Notes

Reaction equation

HRID 1692099 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:33]2[CH:38]=[CH:37][C:36]([C:39]([N:41]3[CH2:46][CH2:45][CH:44]([C:47]([F:50])([F:49])[F:48])[CH2:43][CH2:42]3)=[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].C1COCC1.O.C(O)(C(F)(F)F)=O>C(OCC)(=O)C>[Cl:32][C:6]1[CH:5]=[C:4]([C:33]2[CH:34]=[CH:35][C:36]([C:39]([N:41]3[CH2:46][CH2:45][CH:44]([C:47]([F:50])([F:48])[F:49])[CH2:43][CH2:42]3)=[O:40])=[CH:37][CH:38]=2)[CH:3]=[C:2]([Cl:1])[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 4

HCID 962WaterHCID 6422Trifluoroacetic acidHCID 8028TetrahydrofuranHCID 66904908(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one

Product 1

HCID 17751083(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(4-hydroxy-piperidin-1-yl)-pyrrolidin-2-oneYield 76%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Treat a mixture of (R)-3-[3,5-dichloro-4′-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-1-(4-triisopropylsilanyloxy-piperidin-1-yl)-pyrrolidin-2-one (0.34 g), THF (6 mL) and water (6 mL) with TFA (2 mL) at room temperature for 1 hour and at 50° C. for 2 hours. Cool the reaction, dilute with ethyl acetate, and wash with sodium bicarbonate (sat.). Dry the organic layer (Na2SO4), remove the solvent in vacuo to afford crude product, and purify on silica gel column with 100% ethyl acetate and 10% methanol in methylene chloride to afford 0.205 g (76%) of the titled product. MS (m/z): 598 (M+).

Workup

  1. additionTreat
  2. temperatureCool
  3. customthe reaction
  4. washwash with sodium bicarbonate (sat.)
  5. dry with materialDry the organic layer (Na2SO4)
  6. customremove the solvent in vacuo
  7. customto afford crude product
  8. custompurify on silica gel column with 100% ethyl acetate and 10% methanol in methylene chloride

Sources & evidence

ORD record
ord-cf01e871c67f4a798b60e90b1361c1df
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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