Ethylene Oxide → t-Butyl 3-Methyl-7beta-phenoxyacetamidoceph-3-em-4-carboxylate

HRID 1763809Notes

Reaction equation

HRID 1763809 reaction equation
C1OC1.[NH2:4][C@@H:5]1[C:20](=[O:21])[N:7]2[C:8]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])=[C:9]([CH3:12])[CH2:10][S:11][C@H:6]12.[O:22]([CH2:29][C:30](Cl)=[O:31])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>C(Cl)Cl>[CH3:12][C:9]1[CH2:10][S:11][C@@H:6]2[C@H:5]([NH:4][C:30](=[O:31])[CH2:29][O:22][C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:20](=[O:21])[N:7]2[C:8]=1[C:13]([O:15][C:16]([CH3:17])([CH3:19])[CH3:18])=[O:14]

Participants

5

Reactant 3

HCID 6354Ethylene OxideHCID 69703Phenoxyacetyl chlorideHCID 10869362t-Butyl 7beta-amino-3-methyl-3-cephem-4-carboxylate

Product 1

HCID 15379240t-Butyl 3-Methyl-7beta-phenoxyacetamidoceph-3-em-4-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of ethylene oxide (12 ml) in dry methylene chloride (30 ml) was added to a solution of t-butyl 7β-amino-3-methylceph-3-em-4-carboxylate (52 g, 0.193 mole) in dry methylene chloride (200 ml) cooled in an ice-water bath. A solution of redistilled phenoxyacetyl chloride (33.2 g, 0.194 mole) in dry methylene chloride (25 ml) was added over 2 minutes with stirring. The mixture was stirred for 2 hours, washed with 3% sodium hydrogen carbonate solution (2 × 70 ml), and water, N-hydrochloric acid and brine (70 ml of each), dried and evaporated to a foam. This foam was redissolved in methylene chloride (200 ml) and part (3 ml) of the solution was reevaporated to a white foam (1.13 g), [α]D + 107°, λmax 268.5 nm (ε 7,850) 274.5 nm (ε 7,000), inflexion at 264 nm (ε 7,500), νmax (CHBr3) 3417 (NH), 1786 (azetidin-2-one), 1718 (CO2R) and 1697 and 1530 cm-1 (CONH), τ 0.99 (1H,d, J 8.5 Hz; NH), 2.5 to 3.2 (5H,m; C6H5OCH2), 4.34 (1H,dd, J 8.5, 5 Hz; C7 -H), 4.91 1H,d, J 5 Hz; C6 -H), 5.38 (2H,s; C6H5OCH2), 6.38, 6.66 (2H, AB-q, J 18 Hz; C2 -H2), 8.01 (3H,s; C3 -CH3), 8.52 (9H,s; CO2C(CH3)3) (Found: C, 58.3, 58.4; H, 5.95, 6.0; N, 6.7, 7.0; S, 7.7 C20H24N2O5S (404.5) requires C, 59.4; H, 6.0; N, 6.9; S, 7.7%).

Workup

  1. temperaturecooled in an ice-water bath
  2. stirringThe mixture was stirred for 2 hours
  3. washwashed with 3% sodium hydrogen carbonate solution (2 × 70 ml), and water, N-hydrochloric acid and brine (70 ml of each),
  4. customdried
  5. customevaporated to a foam
  6. dissolutionThis foam was redissolved in methylene chloride (200 ml)
  7. custompart (3 ml) of the solution was reevaporated to a white foam (1.13 g), [α]D + 107°, λmax 268.5 nm (ε 7,850) 274.5 nm (ε 7,000), inflexion at 264 nm (ε 7,500), νmax (CHBr3) 3417 (NH), 1786 (azetidin-2-one), 1718 (CO2R) and 1697 and 1530 cm-1 (CONH), τ 0.99 (1H,d, J 8.5 Hz; NH), 2.5 to 3.2 (5H,m; C6H5OCH2), 4.34 (1H,dd, J 8.5, 5 Hz; C7 -H), 4.91 1H,d

Sources & evidence

ORD record
ord-bb0064beb93e42368ffb8486d526437c
Source dataset
uspto-grants-1978_09
Patent number
US04113591

Reaction notes

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