Diethyl Ether → HCID 21901924, compound

HRID 2110322Notes

Reaction equation

HRID 2110322 reaction equation
Br[CH2:2][C:3]1[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=[C:5]([C:13]([F:16])([F:15])[F:14])[CH:4]=1.[Cl:17][C:18]1[CH:23]=[CH:22][C:21]([C:24]2([C:28]([N:30]3[CH2:35][CH2:34][CH2:33][CH:32]([OH:36])[CH2:31]3)=O)[CH2:27][CH2:26][CH2:25]2)=[CH:20][CH:19]=1.CCOCC.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:14][C:13]([F:16])([F:15])[C:5]1[CH:4]=[C:3]([CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=1)[CH2:2][O:36][CH:32]1[CH2:33][CH2:34][CH2:35][N:30]([CH2:28][C:24]2([C:21]3[CH:22]=[CH:23][C:18]([Cl:17])=[CH:19][CH:20]=3)[CH2:27][CH2:26][CH2:25]2)[CH2:31]1

Participants

6

Reactant 4

HCID 3283Diethyl EtherHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 21226445Aluminium lithium hydrideHCID 21901930HCID 21901930, compound

Product 1

HCID 21901924HCID 21901924, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Following the procedure described in Example 72, 1-Bromomethyl-3,5-bis-trifluoromethyl-benzene was used to alkylate 56 mg (0.19 mmol) of [1-(4-Chloro-phenyl)-cyclobutyl]-(3-hydroxy-piperidin-1-yl)-methanone, forming the ether adduct [3-(3,5-Bis-trifluoromethyl-benzyloxy)-piperidin-1-yl]-[1-(4-chloro-phenyl)-cyclobutyl]-methanone (39 mg, 39%). A portion of this compound (22 mg, 0.043 mmol) was dissolved in 1 mL of THF and excess lithium aluminum hydride (16 mg, ca. 10 equivalents) was added. The solution was heated to reflux for 5 minutes, cooled to 0° C., and quenched by dropwise addition of 0.5 mL 1M NaOH. Additional THF (10 mL) was added, the suspension was stirred at room temperature for 30 minutes, and then was filtered though a plug of sodium sulfate. The solution thus obtained was concentrated in vacuo and the residue was purified by flash chromatography on silica gel using as eluent a gradient of ethyl acetate in hexane containing 1% ammonium hydroxide. 3-(3,5-Bis-trifluoromethyl-benzyloxy)-1-[1-(4-chloro-phenyl)-cyclobutylmethyl]-piperidine, 189, was obtained (12 mg, 56%). Data for this compound: MS 506 (M++1).

Workup

  1. temperatureThe solution was heated
  2. temperatureto reflux for 5 minutes
  3. customquenched by dropwise addition of 0.5 mL 1M NaOH
  4. additionAdditional THF (10 mL) was added
  5. filtrationwas filtered though a plug of sodium sulfate
  6. customThe solution thus obtained
  7. concentrationwas concentrated in vacuo
  8. customthe residue was purified by flash chromatography on silica gel using as eluent a gradient of ethyl acetate in hexane containing 1% ammonium hydroxide

Sources & evidence

ORD record
ord-d3dfe8c9308747aab6e22fa489e9554a
Source dataset
uspto-grants-2009_04
Patent number
US07517892B2

Reaction notes

Loading…