Propylene Oxide → t-Butyl 3-acetoxymethyl-7beta-(pyrid-4-ylacetamido)ceph-3-em-4-carboxylate

HRID 2398156Notes

Reaction equation

HRID 2398156 reaction equation
Cl.[N:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9](Cl)=[O:10])=[CH:4][CH:3]=1.C1OC1C.[C:16]([O:19][CH2:20][C:21]1[CH2:22][S:23][C@@H:24]2[C@H:35]([NH2:36])[C:34](=[O:37])[N:25]2[C:26]=1[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])(=[O:18])[CH3:17]>C(OCC)(=O)C>[C:16]([O:19][CH2:20][C:21]1[CH2:22][S:23][C@@H:24]2[C@H:35]([NH:36][C:9](=[O:10])[CH2:8][C:5]3[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=3)[C:34](=[O:37])[N:25]2[C:26]=1[C:27]([O:29][C:30]([CH3:31])([CH3:32])[CH3:33])=[O:28])(=[O:18])[CH3:17]

Participants

5

Reactant 3

HCID 6378Propylene OxideHCID 15573427tert-butyl (6R,7R)-3-[(acetyloxy)methyl]-7-amino-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateHCID 232920204-Pyridineacetyl chloride hydrochloride

Product 1

HCID 131710773t-Butyl 3-acetoxymethyl-7beta-(pyrid-4-ylacetamido)ceph-3-em-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

A suspension of pyrid-4-ylacetyl chloride hydrochloride (6.0 g.) in ethyl acetate (50 ml) containing propylene oxide (12 ml.) was stirred, cooled in ice and treated dropwise with a solution of t-butyl 3-acetoxymethyl-7β-aminoceph-3-em-4-carboxylate (5.0 g.) in ethyl acetate (50 ml.). The mixture was stirred at 20° for 20 hours and then washed with saturated sodium bicarbonate solution and extracted with 2N hydrochloric acid. The aqueous extract was washed with ethyl acetate, neutralised with saturated sodium bicarbonate solution and extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulphate and evaporated to small bulk whereupon crystallisation began. The crystalline solid was washed well with petroleum spirit (bp. 40°-60°) and dried to give the title ester as a buff coloured powder (5.4 g., 80% based on amine). A portion (250 mg.) was recrystallised from ethyl acetate as white needles (170 mg.), [α]D + 94° (c 0.9, DMSO) λmax. (EtOH) 256.5 nm (ε 9,900), νmax. (CHBr3) 3412 (NH), 1784 (β-lactam), 1736 (OAc), 1722 (CO2R), 1690 and 1512 cm.-1 (CONH), τ (d6 -DMSO) 0.81 (d, J 8 Hz; NH), 1.47 and 2.68 (2d, J 5 Hz; aromatic protons), 4.27 (q, J 8 and 5 Hz; C- 7H), 4.85 (d, J 5 Hz; C-6 H), 5.01 and 5.36 (2d, J 13 Hz; C-3CH2), 6.38 (s; CH2CONH), 6.39 (s; C-2CH2), 7.96 (s; OCOCH3), and 8.50 (s; C(CH3)3).

Workup

  1. temperaturecooled in ice
  2. stirringThe mixture was stirred at 20° for 20 hours
  3. washwashed with saturated sodium bicarbonate solution
  4. extractionextracted with 2N hydrochloric acid
  5. extractionThe aqueous extract
  6. washwas washed with ethyl acetate
  7. extractionextracted with ethyl acetate
  8. washThe extract was washed with water
  9. dry with materialdried over magnesium sulphate
  10. customevaporated to small bulk whereupon crystallisation
  11. washThe crystalline solid was washed well with petroleum spirit (bp. 40°-60°)
  12. customdried

Sources & evidence

ORD record
ord-469d98bd9c484d0c81cb1af13d3dc0a1
Source dataset
uspto-grants-1977_05
Patent number
US04024134

Reaction notes

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