Formaldehyde → HCID 70615964, compound

HRID 2419876Notes

Reaction equation

HRID 2419876 reaction equation
Br[CH2:2][C:3]1[CH2:4][S:5][C@@H:6]2[C@H:17]([NH:18][C:19](=[O:28])[CH2:20][O:21][C:22]3[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=3)[C:16](=[O:29])[N:7]2[C:8]=1[C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10].[C:30]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.P(Br)(Br)Br.C=O.C(=O)([O-])O.[Na+]>C(Cl)Cl>[O:21]([CH2:20][C:19]([NH:18][C@@H:17]1[C:16](=[O:29])[N:7]2[C:8]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])=[C:3]([CH:2]=[CH2:30])[CH2:4][S:5][C@H:6]12)=[O:28])[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

7

Reactant 5

HCID 712FormaldehydeHCID 11776TriphenylphosphineHCID 24614Phosphorus tribromideHCID 516892Sodium BicarbonateHCID 70615395HCID 70615395, compound

Product 1

HCID 70615964HCID 70615964, compoundYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A solution of t-butyl 3-bromomethyl-7β-phenoxyacetamidoceph-3-em-4-carboxylate, 1β-oxide (24.97 g, 50.5 mmole) and triphenylphosphine (16.4 g, 1.25 equiv.) in dry methylene chloride (300 ml) was stirred at ca. 20° for 16 hours and then cooled to --20°. A solution of phosphorus tribromide (7.34 ml, 1.5 equiv.) in dry methylene chloride (100 ml) was added with stirring over a period of 30 minutes with the reaction temperature being maintained at -20°; the mixture was then stirred at this temperature for a further hour. 40%-Formaldehyde solution (190 ml) and saturated aqueous sodium hydrogen carbonate solution (750 ml) were added in one portion, and the two-phase mixture was stirred vigorously while its temperature was allowed to reach 20° and then held at this temperature for a further hour. The organic phase was washed with water, dried (MgSO4), and evaporated, and the residue was chromatographed on Kieselgel G (Merck, 0.05 to 0.2 mm, 800 g), eluting with benzene-ethyl acetate (15:1) and (10:1) (2 liters of each). Appropriate fractions were combined and evaporated to give the title ester as a pale-yellow foam (13.53 g, 63%), [α]D - 44° (C 1.00; Me2SO), λmax (EtOH) 292.5 nm (ε 15,300), inflexions at 269.5 and 276.5 nm (ε 10,000 and 12,400), having a p.m.r. spectrum (Me2SO-d6) similar to that described in Example A (iii) 11(a)

Workup

  1. temperaturecooled to --20°
  2. temperaturebeing maintained at -20°
  3. stirringthe mixture was then stirred at this temperature for a further hour
  4. stirringthe two-phase mixture was stirred vigorously while its temperature
  5. customto reach 20°
  6. waitheld at this temperature for a further hour
  7. washThe organic phase was washed with water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customthe residue was chromatographed on Kieselgel G (Merck, 0.05 to 0.2 mm, 800 g)
  11. washeluting with benzene-ethyl acetate (15:1) and (10:1) (2 liters of each)
  12. customevaporated

Sources & evidence

ORD record
ord-ad0bf1fe29a9494d9d27aca0749c5ee1
Source dataset
uspto-grants-1978_08
Patent number
US04107431

Reaction notes

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