Potassium Carbonate → (5R,6S)-3-[(E)-2-{(2 S)-1-acetimidoylpyrrolidin-2-yl}-1-methylethenyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

HRID 1090549Notes

Reaction equation

HRID 1090549 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](/[C:15](/[CH3:22])=[CH:16]/[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1)=[C:8]2[C:12]([OH:14])=[O:13])[CH3:3].C(=O)([O-])[O-].[K+].[K+].Cl.[C:30](=[NH:35])(OCC)[CH3:31]>O>[C:30]([N:18]1[CH2:19][CH2:20][CH2:21][C@H:17]1/[CH:16]=[C:15](/[C:7]1[CH2:6][C@H:5]2[N:9]([C:10](=[O:11])[C@@H:4]2[C@H:2]([OH:1])[CH3:3])[C:8]=1[C:12]([OH:14])=[O:13])\[CH3:22])(=[NH:35])[CH3:31]

Participants

5

Reactant 3

HCID 11430Potassium Carbonate2×HCID 2724290Ethanimidic acid, ethyl ester, hydrochloride (1:1)HCID 10086476(5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(E)-2-{(2S)-pyrrolidin-2-yl}-1-methylethenyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid

Product 1

HCID 15702907(5R,6S)-3-[(E)-2-{(2 S)-1-acetimidoylpyrrolidin-2-yl}-1-methylethenyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acidYield 48.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

A solution of (5R,6S)-6-[(1R)-1-hydroxyethyl]-7-oxo-3-[(E)-2-{(2S)-pyrrolidin-2-yl}-1-methylethenyl]-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (0.44 g) in water (30 ml) was adjusted to pH 8.5 with aqueous potassium carbonate at 0° C. and ethyl acetimidate hydrochloride (5.4 g) was added in portions while adjusting around pH 8.5 with addition of aqueous potassium carbonate. After stirring for 15 minutes at pH 8.5, the reaction mixture was washed with a mixture of ethyl acetate and tetrahydrofuran (9:1 V/V, 150 ml), and concentrated in vacuo. The residue was chromatographed on nonionic adsorption resin "Diaion HP-20" (Trademark, made by Mitsubishi Chemical Industries) (80 ml) eluting successively with water (200 ml) and 5% aqueous isopropyl alcohol (200 ml). The fractions containing the desired compound were collected and lyophilized to give (5R,6S)-3-[(E)-2-{(2 S)-1-acetimidoylpyrrolidin-2-yl}-1-methylethenyl]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (241 mg).

Workup

  1. washthe reaction mixture was washed with a mixture of ethyl acetate and tetrahydrofuran (9:1 V/V, 150 ml)
  2. concentrationconcentrated in vacuo
  3. customThe residue was chromatographed on nonionic adsorption resin "Diaion
  4. wash" (Trademark, made by Mitsubishi Chemical Industries) (80 ml) eluting successively with water (200 ml) and 5% aqueous isopropyl alcohol (200 ml)
  5. additionThe fractions containing the desired compound
  6. customwere collected

Sources & evidence

ORD record
ord-1cc8851626c54401a8bd5d4a4be82dc3
Source dataset
uspto-grants-1992_01
Patent number
US05081237

Reaction notes

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