Hydrochloric Acid → (R)-1-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-propan-1-ol

HRID 1172673Notes

Reaction equation

HRID 1172673 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([C@H:25]([O:28]C(=O)[C@H](OC)C3C=CC=CC=3)[CH2:26][CH3:27])=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([C:21]([F:24])([F:23])[F:22])[CH2:17][CH2:16]3)[N:13]=2)=[CH:5][CH:4]=1.[OH-].[Na+].Cl>O1CCCC1.C(O)C.O>[F:41][C:2]([F:1])([F:40])[C:3]1[CH:8]=[CH:7][C:6]([C:9]2[S:10][C:11]([C@H:25]([OH:28])[CH2:26][CH3:27])=[C:12]([CH2:14][N:15]3[CH2:20][CH2:19][CH:18]([C:21]([F:23])([F:22])[F:24])[CH2:17][CH2:16]3)[N:13]=2)=[CH:5][CH:4]=1

Participants

7

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59556389(R)-methoxy-phenyl-acetic acid (R)-1-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-propyl ester

Product 1

HCID 59556315(R)-1-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-propan-1-olYield 53.5%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 0.67 g of (R)-methoxy-phenyl-acetic acid (R)-1-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-propyl ester in 2.5 mL of tetrahydrofuran and 2.5 mL of ethanol at 0° C. was dropwise added 3.5 mL of a molar solution of sodium hydroxide in 2.7 mL of water. The resulting mixture was stirred at 0° C. for 15 minutes then 0.6 mL of a 5N solution of hydrochloric acid in 2.7 mL of water was added. After removal of the organic solvents under vacuum, the mixture was extracted with dichloromethane, filtered through a silicone treated filter and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (dichloromethane 90/ethyl acetate 10) to give 270 mg of (R)-1-[2-(4-trifluoromethyl-phenyl)-4-(4-trifluoromethyl-piperidin-1-ylmethyl)-thiazol-5-yl]-propan-1-ol.

Workup

  1. customat 0° C.
  2. customAfter removal of the organic solvents under vacuum
  3. extractionthe mixture was extracted with dichloromethane
  4. filtrationfiltered through a silicone
  5. additiontreated
  6. filtrationfilter
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by column chromatography on silica gel (dichloromethane 90/ethyl acetate 10)

Sources & evidence

ORD record
ord-fabbaa1827f04a0ea420ff84b9e51fd6
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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