Sodium borohydride → 4-Benzyl-2,2,6,6-tetramethylmorpholine

HRID 601556Notes

Reaction equation

HRID 601556 reaction equation
[BH4-].[Na+].[CH2:3]([N:10]1[CH2:15][C:14]([CH3:17])([CH3:16])[O:13][C:12]([CH2:19]I)([CH3:18])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1>CS(C)=O>[CH2:3]([N:10]1[CH2:15][C:14]([CH3:17])([CH3:16])[O:13][C:12]([CH3:19])([CH3:18])[CH2:11]1)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

4

Reactant 2

HCID 4311764Sodium borohydride2×HCID 574214974-Benzyl-2-(iodomethyl)-2,6,6-trimethylmorpholine

Product 1

HCID 122829994-Benzyl-2,2,6,6-tetramethylmorpholineYield 60.2%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
100 °C

Procedure

Add solid NaBH4 (776 mg, 20.5 mmol) to a solution of 4-benzyl-2-iodomethyl-2,6,6-trimethyl-morpholine (6.22 g, 17.3 mmol) in DMSO (20 mL) and then heat the mixture at 100° C. After 2 h, add additional DMSO (10 mL). After an additional 1.25 h, add extra NaBH4 (120 mg, 3.17 mmol). Remove the heat after an additional 1.25 h (total reaction time=4.5 h). Quench the excess NaBH4 with 5 M HCl (20 ml). After 15 min, add 5 M NaOH (20 mL) and 1 M Na2S2O3 (20 mL) and then stir the mixture overnight. Dilute the mixture with tert-butyl methyl ether (250 mL) and water (100 mL). Separate the organic solution and wash with additional water (4×100 mL). Dry, filter and concentrate the organic solution. Purify the residue by flash chromatography, using a gradient from 50% to 100% CH2Cl2 in pentane as eluent. Dry the product so obtained briefly at 60° C. under vacuum to give the title compound (2.43 g, 60%) as a colorless liquid. 1H NMR (400 MHz, DMSO-d6): δ 7.2-7.4 (5H, m), 3.45 (2H, s), 2.12 (4H, s), 1.15 (12H, s).

Workup

  1. waitAfter an additional 1.25 h
  2. customRemove the
  3. temperatureheat after an additional 1.25 h (total reaction time=4.5 h)
  4. customQuench the excess NaBH4 with 5 M HCl (20 ml)
  5. waitAfter 15 min
  6. additionadd 5 M NaOH (20 mL) and 1 M Na2S2O3 (20 mL)
  7. additionDilute the mixture with tert-butyl methyl ether (250 mL) and water (100 mL)
  8. customSeparate the organic solution
  9. washwash with additional water (4×100 mL)
  10. customDry
  11. filtrationfilter
  12. concentrationconcentrate the organic solution
  13. customPurify the residue by flash chromatography
  14. customDry the product
  15. customso obtained briefly at 60° C. under vacuum

Sources & evidence

ORD record
ord-f17c6e1198d4434197880c42bf71b55d
Source dataset
uspto-grants-2011_03
Patent number
US07902356B2

Reaction notes

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