Sodium Hydroxide → (R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-5-hydroxy-dihydro-furan-2-one

HRID 1692116Notes

Reaction equation

HRID 1692116 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:23]=[CH:22][C:21]([C:24]([N:26]3[CH2:31][CH2:30][CH:29]([C:32]([F:35])([F:34])[F:33])[CH2:28][CH2:27]3)=[O:25])=[CH:20][CH:19]=2)[CH:5]=[C:6]([Cl:17])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][C@@H:12](CO)[O:11][C:10]1=[O:16].[OH-].[Na+].CC[O:40]C(C)=O.CCCCCCC.I(O)(=O)(=O)=O>C1COCC1.O.Cl>[Cl:1][C:2]1[CH:3]=[C:4]([C:18]2[CH:19]=[CH:20][C:21]([C:24]([N:26]3[CH2:27][CH2:28][CH:29]([C:32]([F:34])([F:35])[F:33])[CH2:30][CH2:31]3)=[O:25])=[CH:22][CH:23]=2)[CH:5]=[C:6]([Cl:17])[C:7]=1[CH2:8][C@@H:9]1[CH2:13][CH:12]([OH:40])[O:11][C:10]1=[O:16]

Participants

8

Reactant 4

HCID 14798Sodium HydroxideHCID 65185Metaperiodic acidHCID 21899848Ethylacetate heptane2×HCID 57672058HCID 57672058, compound

Product 1

HCID 57672055(R)-3-[3,5-Dichloro-4'-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-5-hydroxy-dihydro-furan-2-oneYield 68%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Dissolve (3R,5S)-3-[3,5-Dichloro-4′-(4-trifluoromethyl-piperidine-1-carbonyl)-biphenyl-4-ylmethyl]-5-hydroxymethyl-dihydro-furan-2-one (1.5 g, 1 eq.) in THF (10 mL) and then add 2 N NaOH (3 mL). Allow the reaction to stir at room temperature for 1 hour with vigorous stirring. TLC (50% EtOAc/Heptane) shows the complete consumption of starting material. Add dropwise a solution of periodic acid (1.5 g, 2.3 eq.) in water (5 mL). The reaction becomes a white slurry with a small exotherm. After ˜1 hour, TLC (50% EtOAc/Heptane) shows that the reaction is finished. Dilute the slurry with 1 N HCl (10 mL) and extract 3 times with EtOAc (150 mL total). Dry the organic layer and concentrate to give the titled compound as a white foamy solid (1 g, 68% yield).

Workup

  1. customthe reaction
  2. customthe complete consumption of starting material
  3. waitAfter ˜1 hour
  4. extractionextract 3 times with EtOAc (150 mL total)
  5. customDry the organic layer
  6. concentrationconcentrate

Sources & evidence

ORD record
ord-e6daf78a27bc48a79bab4e3c4e56939d
Source dataset
uspto-grants-2012_04
Patent number
US08153807B2

Reaction notes

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