Sodium borohydride → Benzyl 2-(1-hydroxyethyl)morpholine-4-carboxylate

HRID 429284Notes

Reaction equation

HRID 429284 reaction equation
[C:1]([CH:4]1[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]1)(=[O:3])[CH3:2].[BH4-].[Na+]>C1COCC1.CCO>[OH:3][CH:1]([CH:4]1[O:9][CH2:8][CH2:7][N:6]([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:5]1)[CH3:2]

Participants

4

Reactant 2

HCID 4311764Sodium borohydrideHCID 18354411Phenylmethyl 2-acetyl-4-morpholinecarboxylate

Product 1

HCID 18354365Benzyl 2-(1-hydroxyethyl)morpholine-4-carboxylate

Reagents, catalysts & solvents 1

HCID 21873804Tetrahydrofuran ethanolSolvent

Procedure

To a solution of 1.38 of 2-acetyl-4-benzyloxycarbonylmorpholine in 50 mL of 1:1 THF-EtOH was added 400 mg of sodium borohydride, in several portions. The mixture was stirred at room temperature for 2 h, then quenched by addition of 25 mL of saturated NaHCO3. The mixture was diluted with 75 mL of water and 25 mL of EtOAc. The phases were separated and the aqueous phase was extracted with 2×25 mL of EtOAc. The combined organics were washed with 25 mL of brine, dried over Na2SO4, and concentrated. The residue was purified by flash chromatography, eluting with 2:1 hexanes-EtOAc, to yield 383 mg of diastereomer 1, 341 mg of diastereomer 2, and 436 mg of a mixture of the two isomers. Data for diastereomer 1. Rf 0.35 (1:1 hexanes-EtOAc) 1H NMR (500 MHz, CDCl3): δ7.30-7.43 (m, 4H), 5.12-5.23 (m, 2H), 3.80-4.18 (m, 4H), 3.57 (br t, J=11.0Hz, 1H), 3.32 (br s, 1H), 2.84-3.11 (m, 2H), 2.05 (br s, 1H),1.22 (d, J=6.5 Hz, 3H). Data for diastereomer 2. Rf 0.28 (1:1 hexanes-EtOAc).

Workup

  1. customquenched by addition of 25 mL of saturated NaHCO3
  2. additionThe mixture was diluted with 75 mL of water and 25 mL of EtOAc
  3. customThe phases were separated
  4. extractionthe aqueous phase was extracted with 2×25 mL of EtOAc
  5. washThe combined organics were washed with 25 mL of brine
  6. dry with materialdried over Na2SO4
  7. concentrationconcentrated
  8. customThe residue was purified by flash chromatography
  9. washeluting with 2:1 hexanes-EtOAc

Sources & evidence

ORD record
ord-0fb93f4ebc3b4b3b97dc18ca024da03a
Source dataset
uspto-grants-2001_11
Patent number
US06316444B1

Reaction notes

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