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

HRID 1692117Notes

Reaction equation

HRID 1692117 reaction equation
[NH2:1][N:2]1[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]1.[Cl:9][C:10]1[CH:11]=[C:12]([C:25]2[CH:30]=[CH:29][C:28]([C:31]([N:33]3[CH2:38][CH2:37][CH:36]([C:39]([F:42])([F:41])[F:40])[CH2:35][CH2:34]3)=[O:32])=[CH:27][CH:26]=2)[CH:13]=[C:14]([Cl:24])[C:15]=1[CH2:16][C@@H:17]1[CH2:21][CH:20](O)[O:19][C:18]1=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(#N)C>[Cl:24][C:14]1[CH:13]=[C:12]([C:25]2[CH:26]=[CH:27][C:28]([C:31]([N:33]3[CH2:38][CH2:37][CH:36]([C:39]([F:42])([F:41])[F:40])[CH2:35][CH2:34]3)=[O:32])=[CH:29][CH:30]=2)[CH:11]=[C:10]([Cl:9])[C:15]=1[CH2:16][C@@H:17]1[CH2:21][CH2:20][N:1]([N:2]2[CH2:7][CH2:6][CH:5]([OH:8])[CH2:4][CH2:3]2)[C:18]1=[O:19]

Participants

5

Reactant 3

HCID 5049666Sodium triacetoxyborohydrideHCID 121256451-Aminopiperidin-4-OLHCID 57672055(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-5-hydroxy-dihydro-furan-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 20.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

Dissolve 1-Amino-piperidin-4-ol (0.204 g, 1.1 eq.) in acetonitrile (3 mL) and heat the solution to 50° C. When the temperature reaches 35° C., add (R)-3-[3,5-Dichloro-4′-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-5-hydroxy-dihydro-furan-2-one (0.829 g, 1 eq.) and continue heating to 50° C. for 1 hour. Allow the reaction to cool to room temperature and add sodium triacetoxyborohydride (0.508 g, 1.5 eq.). Allow the reaction to stir overnight at room temperature. Add water and extract with EtOAc. Remove the solvent and chromatograph the residue on silica gel to afford 200 mg of the titled compound. MS (m/z): 598 (M+1, 35Cl), 600 (M+1, 37Cl).

Workup

  1. customreaches 35° C.
  2. temperaturecontinue heating to 50° C. for 1 hour
  3. customthe reaction
  4. temperatureto cool to room temperature
  5. customthe reaction
  6. extractionAdd water and extract with EtOAc
  7. customRemove the solvent and chromatograph the residue on silica gel

Sources & evidence

ORD record
ord-b8b15bbf0f64454693c7ad9416da9e28
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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