Sodium hydride → 2-[(Benzyloxy)methyl]-4-tert-butylmorpholine

HRID 603259Notes

Reaction equation

HRID 603259 reaction equation
[CH2:1]([O:8][CH2:9][CH:10]([OH:20])[CH2:11][N:12]([C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:13][CH2:14]O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].C1(C)C=CC(S(C2NC=CN=2)(=O)=O)=CC=1>C1COCC1>[CH2:1]([O:8][CH2:9][CH:10]1[O:20][CH2:14][CH2:13][N:12]([C:16]([CH3:17])([CH3:18])[CH3:19])[CH2:11]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 202744982-Tosyl-1H-imidazoleHCID 576568621-(Benzyloxy)-3-(tert-butyl(2-hydroxyethyl)amino)propan-2-ol

Product 1

HCID 576569302-[(Benzyloxy)methyl]-4-tert-butylmorpholineYield 90.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 1-(benzyloxy)-3-[tert-butyl(2-hydroxyethyl)amino]propan-2-ol (100 mg) in THF (20 mL) was stirred at room temperature under argon. Sodium hydride (60%, 35 mg) was added and the mixture was stirred for 2 hours. The mixture was cooled to ice bath temperature and para-toluenesulfonyl imidazole (79 mg) was added. After 30 minutes the mixture was warmed to room temperature and stirred overnight. The reaction was quenched with saturated aqueous ammonium chloride and then partitioned between 1:1 brine/saturated aqueous sodium hydrogen carbonate and ethyl acetate. The organic layer was washed with 1:1 brine/saturated aqueous sodium hydrogen carbonate, dried (MgSO4), filtered and concentrated at reduced pressure. The residue was purified on the Isco™ Companion (12 g column: 0-10% MeOH in DCM) to give the title compound as a colourless oil (85 mg).

Workup

  1. additionwas added
  2. stirringstirred overnight
  3. customThe reaction was quenched with saturated aqueous ammonium chloride
  4. custompartitioned between 1:1 brine/saturated aqueous sodium hydrogen carbonate and ethyl acetate
  5. washThe organic layer was washed with 1:1 brine/saturated aqueous sodium hydrogen carbonate
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated at reduced pressure
  9. customThe residue was purified on the Isco™ Companion (12 g column: 0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-80a8b8d3c10a44ff859f6891c0c521d8
Source dataset
uspto-grants-2011_03
Patent number
US07906645B2

Reaction notes

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