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

HRID 258651Notes

Reaction equation

HRID 258651 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:30]([O:29][C:27]([C:26]1[N:25]2[C:34](=[O:37])[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@H:24]2[S:23][CH2:22][C:21]=1[CH2:20][O:19][C:16](=[O:18])[CH3:17])=[O:28])([CH3:33])([CH3:31])[CH3:32]

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 2 N 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-2H2), 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 2 N 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-08b6ed9c33d54ffe867cfd76cd7c8c4f
Source dataset
uspto-grants-1977_07
Patent number
US04033950

Reaction notes

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