Methanol → t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylate

HRID 6290

Reaction equation

HRID 6290 reaction equation
P(Cl)(Cl)(Cl)(Cl)Cl.[O:7]=[C:8]1[CH2:12][CH2:11][C@@H:10]([C:13]2[CH2:14][S:15][C@@H:16]3[C@H:27]([NH:28]C(=O)COC4C=CC=CC=4)[C:26](=[O:39])[N:17]3[C:18]=2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[O:9]1.CN1CCOCC1.CO>ClCCl.O>[NH2:28][C@@H:27]1[C:26](=[O:39])[N:17]2[C:18]([C:19]([O:21][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:20])=[C:13]([C@H:10]3[O:9][C:8](=[O:7])[CH2:12][CH2:11]3)[CH2:14][S:15][C@H:16]12

Participants

7

Reactant 4

HCID 887MethanolHCID 79724-MethylmorpholineHCID 24819Phosphorus pentachlorideHCID 57285999t-butyl (6R,7R)-3-[(5S)-2-oxotetrahydrofuran-5-yl]-7-phenoxyacetamido-ceph-3-em-4-carboxylate

Product 1

HCID 57283631t-butyl (6R,7R)-7-amino-3-[(5S)-2-oxotetrahydrofuran-5-yl]ceph-3-em-4-carboxylateYield 40.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Conditions

Temperature
-15 °C

Procedure

Phosphorus pentachloride (0.35 g,1.7 mmol) in dichloromethane (9 ml) was added to t-butyl (6R,7R)-3-[(5S)-2-oxotetrahydrofuran-5-yl]-7-phenoxyacetamido-ceph-3-em-4-carboxylate (0.526 g, 1.1 mmol) and N-methylmorpholine (0.24 ml, 2.2 mmol) in dichloromethane (15 ml) at <-20° C. The reaction was stirred at -15±5° C. for 0.75 h then methanol (3 ml) was added. Stirring was continued for 0.75 h without further cooling and then water (10 ml) was added and the mixture was stirred vigorously for 1 h. The dichloromethane was removed in vacuo, ethyl acetate (ca 10 ml) added, the mixture adjusted to pH5.5 with dilute ammonium hydroxide solution and extracted twice with ethyl acetate. The extracts were washed with brine, dried, concentrated and flash chromatographed, eluting with 40,50,75% ethyl acetate in hexane, to give the title compound as a foam (0.15 g,40%); (Found: M+, 340.1097. C15H20N2O5S requires M, 340.1093); νmax (CH2Cl2) 1770,1710,1362,1350,1235 and 1170 cm-1 ; δH (CDCl3) 1.54 (9H,s), 1.9-2.1 (1H,m), 2.5-2.8 (3H,m), 3.27 and 3.56 (2H,ABq,J18.5 Hz), 4.80 (1H,d,J5Hz), 4.96 (1H,d,J5 Hz), 5.6-5.7 (1H,m).

Workup

  1. stirringStirring
  2. waitwas continued for 0.75 h
  3. temperaturewithout further cooling
  4. stirringthe mixture was stirred vigorously for 1 h
  5. customThe dichloromethane was removed in vacuo, ethyl acetate (ca 10 ml)
  6. additionadded
  7. extractionextracted twice with ethyl acetate
  8. washThe extracts were washed with brine
  9. customdried
  10. concentrationconcentrated
  11. customflash chromatographed
  12. washeluting with 40,50,75% ethyl acetate in hexane

Sources & evidence

ORD record
ord-9ec0a0a647af429cbc50491e9b181fb6
Source dataset
uspto-grants-1993_09
Patent number
US05246926

Linked notes

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