Borane → tert-Butyl 2-(hydroxymethyl)morpholine-4-carboxylate

HRID 1864001Notes

Reaction equation

HRID 1864001 reaction equation
[CH3:1][C:2]([O:5][C:6]([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14](O)=[O:15])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].B>C1COCC1>[OH:15][CH2:14][CH:10]1[O:11][CH2:12][CH2:13][N:8]([C:6]([O:5][C:2]([CH3:4])([CH3:3])[CH3:1])=[O:7])[CH2:9]1

Participants

4

Reactant 2

HCID 6331BoraneHCID 27559654-((Tert-butoxy)carbonyl)morpholine-2-carboxylic acid

Product 1

HCID 5201202tert-Butyl 2-(hydroxymethyl)morpholine-4-carboxylateYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-{[(1,1-dimethylethyl)oxy]carbonyl}-2-morpholinecarboxylic acid (2.0 g, 21.6 mmol) in THF (45 mL) was cooled to 0° C. A solution of borane (39 mL, 39.0 mmol, 1M in THF) was added over 25 min via addition funnel. After warming to RT, the reaction was quenched by dropwise addition of methanol/acetic acid (18 mL, 9:1 v/v). The solvent was removed under reduced pressure and the residue partitioned between ethyl acetate and 1N HCl. The aqueous layer was extracted with ethyl acetate and combined extracts were washed with water, 1N NaOH, water, brine and dried over sodium sulfate. Removal of the solvent under reduced pressure afforded 1.83 g (97%) of the desired material. 1H NMR (400 MHz, CDCl3) δ ppm 1.49 (s, 9H) 2.30 (br d, J=11.37 Hz, 1H) 2.69-2.79 (m, J=9.51, 6.41, 3.28, 3.28 Hz, 1H) 2.84 (ddd, J=13.77, 10.86, 3.16 Hz, 2H) 3.27-3.38 (m, 1H) 3.47 (br s, 1H) 3.63-3.75 (m, 2H) 4.10-4.19 (m, 1H) 4.27 (br s, 1H).

Workup

  1. customthe reaction was quenched by dropwise addition of methanol/acetic acid (18 mL, 9:1 v/v)
  2. customThe solvent was removed under reduced pressure
  3. customthe residue partitioned between ethyl acetate and 1N HCl
  4. extractionThe aqueous layer was extracted with ethyl acetate
  5. washwere washed with water, 1N NaOH, water, brine
  6. dry with materialdried over sodium sulfate
  7. customRemoval of the solvent under reduced pressure

Sources & evidence

ORD record
ord-9ed36284c879445f8bdb314c8e9ca2b7
Source dataset
uspto-grants-2009_12
Patent number
US07625890B2

Reaction notes

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