Sodium hydride → HCID 22860775, compound

HRID 582097Notes

Reaction equation

HRID 582097 reaction equation
[H-].[Na+].[CH2:3]([N:10]1[CH2:15][CH2:14][O:13][C@H:12]([OH:16])[C@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[F:23][C:24]([F:38])([F:37])[C:25]1[CH:26]=[C:27]([CH:30]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:32]=1)[CH2:28]Br.C([O-])(O)=O.[Na+]>C1COCC1.[I-].C([N+](CCCC)(CCCC)CCCC)CCC>[CH2:3]([N:10]1[CH2:15][CH2:14][O:13][C@H:12]([O:16][CH2:28][C:27]2[CH:30]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:32]=[C:25]([C:24]([F:23])([F:37])[F:38])[CH:26]=2)[C@H:11]1[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 24758Sodium hydrideHCID 1225733,5-Bis(trifluoromethyl)benzyl bromideHCID 516892Sodium BicarbonateHCID 22860777HCID 22860777, compound

Product 1

HCID 22860775HCID 22860775, compoundYield 59.1%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a suspension of 0.592 g (14.8 mmol) of NaH in 30 mL of dry THF at 0° C. was added 3.32 g (12.3 mmol) of 4-benzyl-2-(S)-hydroxy-3-(R)-phenyl-morpholine prepared in step A. After 15 min 0.915 g of tetrabutylammonium iodide (2.47 mmol) and 2.4 mL (13 mmol) of 3,5-bis(trifluoromethyl)benzyl bromide were added. The resulting mixture was stirred at ice-bath temperature for 1 h, then poured into saturated NaHCO3 solution and extracted with ethyl acetate (EtOAc). The organic layers were combined, washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the resiue was chromatographed on a Waters Prep500 HPLC system using 50% EtOAc/Hexane to isolate 3.6 g (59%) of 4-Benzyl-2-(S)-(3,5-bis(trifluoromethyl)benzyloxy)-3-(R)-phenylmorpholine.

Workup

  1. extractionextracted with ethyl acetate (EtOAc)
  2. washwashed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationThe filtrate was concentrated in vacuo
  6. customthe resiue was chromatographed on a Waters Prep500 HPLC system

Sources & evidence

ORD record
ord-3f3e918c0f394fe791ecf88fdbf5bc13
Source dataset
uspto-grants-1999_07
Patent number
US05922706

Reaction notes

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