Hydrochloric Acid → (5R,6S)-3-(1-acetimidoylpyrrolidin-3-yl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 1029690Notes

Reaction equation

HRID 1029690 reaction equation
[OH:1][C@@H:2]([C@H:4]1[C:10](=[O:11])[N:9]2[C@@H:5]1[CH2:6][C:7]([CH:15]1[CH2:19][CH2:18][NH:17][CH2:16]1)=[C:8]2[C:12]([OH:14])=[O:13])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Cl.[C:27](=[NH:32])(OCC)[CH3:28].Cl>P([O-])([O-])([O-])=O>[C:27]([N:17]1[CH2:18][CH2:19][CH:15]([C:7]2[CH2:6][C@H:5]3[N:9]([C:10](=[O:11])[C@@H:4]3[C@H:2]([OH:1])[CH3:3])[C:8]=2[C:12]([OH:14])=[O:13])[CH2:16]1)(=[NH:32])[CH3:28]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium Carbonate2×HCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 15117376(5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-(pyrrolidin-3-yl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Product 1

HCID 15117449(5R,6S)-3-(1-acetimidoylpyrrolidin-3-yl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidYield 38.5%

Reagents, catalysts & solvents 1

HCID 1061PhosphateSolvent

Conditions

Temperature
0 °C

Procedure

A solution of (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-(pyrrolidin-3-yl)-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (180 mg) in phosphate buffer solution (pH was adjusted to around pH 8.5 with 30% aqueous potassium carbonate at 0° C. To the solution was added four portions of ethyl acetimidate hydrochloride (835 mg), while adjusting pH to around 8.5 with j0% aqueous potassium carbonate. After stirring for 10 minutes at 0° C., the solution was adjusted to around pH 7.0 with 1N hydrochloric acid. After the mixture was washed with a mixture of ethyl acetate (270 ml) and tetrahydrofuran (30 ml), the aqueous layer was concentrated. The resulting solution was chromatographed on nonionic adsorption resin "Diaion HP-20" (40 ml) eluting with a mixture of acetonitrile and water (2:98, V/V). The fractions containing the object compound were collected and freeze-dried to give (5R,6S)-3-(1-acetimidoylpyrrolidin-3-yl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (80 mg).

Workup

  1. washAfter the mixture was washed with a mixture of ethyl acetate (270 ml) and tetrahydrofuran (30 ml)
  2. concentrationthe aqueous layer was concentrated
  3. customThe resulting solution was chromatographed on nonionic adsorption resin "Diaion
  4. wash" (40 ml) eluting with a mixture of acetonitrile and water (2:98, V/V)
  5. additionThe fractions containing the object compound
  6. customwere collected
  7. customfreeze-dried

Sources & evidence

ORD record
ord-44c2a2fe68944947a6d40435a11f2efa
Source dataset
uspto-grants-1992_04
Patent number
US05102877

Reaction notes

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