4-Methylmorpholine → HCID 11074788, compound

HRID 1066026Notes

Reaction equation

HRID 1066026 reaction equation
[Si:1]([N:8]1[C:11](=[O:12])[CH2:10][C@@H:9]1[C:13](O)=[O:14])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>C1COCC1.O.CCOC(C)=O>[Si:1]([N:8]1[C@@H:9]([CH2:13][OH:14])[CH2:10][C:11]1=[O:12])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 2733822(R)-1-(tert-Butyldimethylsilyl)-4-oxoazetidine-2-carboxylic acidHCID 4311764Sodium borohydride

Product 1

HCID 11074788HCID 11074788, compoundYield 60.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 1-(tert-butyldimethylsilyl)-4-oxoazetidine-2(R)-carboxylic acid (15.0 g, 65.40 mmol) in THF (367 mL) at 0°, was added N-methylmorpholine (7.2 mL, 65.40 mmol) and isobutyl chloroformate (8.5 mL, 65.40 mmol). After stirring for 1.5 h at 0° a solution of NaBH4 (9.9 g, 261.61 mmol) in H2O (98 mL) was added portionwise. The reaction was stirred for 45 min, then diluted with EtOAc and quenched with aqueous HCl solution (10%) to pH 5-6. The organic phase was collected and the aqueous phase was extracted twice with EtOAc. The combined organic layers were washed with saturated aqueous NaHCO3 and brine, dried (MgSO4), filtered and concentrated. The residual oil was purified by flash chromatography (SiO2, eluent:gradient 25% to 50% EtOAc/hexane) to provide 1-(tert-butyldimethylsilyl)-4(R)-(hydroxymethyl)azetidin-2-one (8.46 g, 60% yield) as a white solid. 1H-NMR (400 MHz, CDCl3) δ3.74-3.69 (m, 1H), 3.65-3.56 (m, 2H), 3.1-2.98 (m, 1H), 2.81-2.76 (m, 1H), 2.01 (s, 1H), 0.89 (s, 9H), 0.18 (s, 3H), 0.16 (s, 3H). FAB MS m/z 216.2 (MH+).

Workup

  1. additionwas added portionwise
  2. customquenched with aqueous HCl solution (10%) to pH 5-6
  3. customThe organic phase was collected
  4. extractionthe aqueous phase was extracted twice with EtOAc
  5. washThe combined organic layers were washed with saturated aqueous NaHCO3 and brine
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residual oil was purified by flash chromatography (SiO2, eluent:gradient 25% to 50% EtOAc/hexane)

Sources & evidence

ORD record
ord-3bb3168327344b0aa86dd8041e8726d3
Source dataset
uspto-grants-2001_06
Patent number
US06242439B1

Reaction notes

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