4-Methylmorpholine → (2S,5R)-6-(benzyloxy)-2-(hydroxymethyl)-1,6-diazabicyclo[3.2.1]octan-7-one

HRID 57335Notes

Reaction equation

HRID 57335 reaction equation
[Na].[CH2:2]([O:9][N:10]1[C:16](=[O:17])[N:15]2[CH2:18][C@H:11]1[CH2:12][CH2:13][C@H:14]2[C:19](O)=[O:20])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.CN1CCOCC1.ClC(OCC)=O.[BH4-].[Na+]>O1CCCC1.C(OCC)(=O)C.O>[CH2:2]([O:9][N:10]1[C:16](=[O:17])[N:15]2[CH2:18][C@H:11]1[CH2:12][CH2:13][C@H:14]2[CH2:19][OH:20])[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

9

Reactant 5

HCID 79724-MethylmorpholineHCID 10928Ethyl chloroformateHCID 4311764Sodium borohydrideHCID 5360545SodiumHCID 57389355(2S,5R)-6-(Benzyloxy)-7-oxo-1,6-diazabicyclo[3.2.1]octane-2-carboxylic acid

Product 1

HCID 86700666(2S,5R)-6-(benzyloxy)-2-(hydroxymethyl)-1,6-diazabicyclo[3.2.1]octan-7-oneYield 99%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

The sodium salt of (2S, 5R)-6-benzyloxy-7-oxo-1, 6-diaza-bicyclo [3.2.1] octane-2-carboxylic acid (II) (50 g, 0.16 moles, prepared as per the procedure described in Indian Patent Application No. 699/MUM/2013) was suspended in tetrahydrofuran (500 ml). To the suspension was added N-methyl morpholine (18.4 ml, 0.16 moles) under stirring. The reaction mixture was cooled to about −10° C. and ethyl chloroformate was added via addition funnel and stirred for 1 hour at about −10° C. To the reaction mixture was added NaBH4 (9.56 g, 0.25 moles) in lots under stirring. The reaction was monitored with the help of thin layer chromatography (TLC). After completion of reaction, water (500 ml) followed by ethyl acetate (500 ml) was added to the reaction mass. The reaction mixture was stirred for 30 minutes and the layers were separated. Organic layer was washed with brine (200 ml). The solvent was evaporated under vacuum to dryness to provide 43 g of (2S, 5R)-6-(benzyloxy)-2-(hydroxymethyl)-7-oxo-1,6-diaza-bicyclo[3.2.1] octane (III) as a pale yellow oil (99% yield).

Workup

  1. stirringstirred for 1 hour at about −10° C
  2. stirringunder stirring
  3. additionwas added to the reaction mass
  4. stirringThe reaction mixture was stirred for 30 minutes
  5. customthe layers were separated
  6. washOrganic layer was washed with brine (200 ml)
  7. customThe solvent was evaporated under vacuum to dryness

Sources & evidence

ORD record
ord-394e63b6b0ae4abaae3a434dc8be9b52
Source dataset
uspto-grants-2016_09
Patent number
US09434728B1

Reaction notes

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