3-Nitrobenzyl alcohol → 4-Methoxybenzyl (6R,7R)-3-(5-acetoxymethyl-tetrahydrofuran-2-yl)-7-phenylacetamidoceph-3-em-4-carboxylate

HRID 612312

Reaction equation

HRID 612312 reaction equation
[PH5].[C:2]([O:5][CH2:6][C@@H:7]1[O:11][C@H:10]([C:12]2[CH2:13][S:14][C@@H:15]3[C@H:31]([NH:32][C:33](=[O:41])[CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:30](=[O:42])[N:16]3[C:17]=2[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[O:19])[CH2:9][CH2:8]1)(=[O:4])[CH3:3].[N+](C1C=C(C=CC=1)CO)([O-])=O.C([O-])(=O)C.[Na+]>C1(C)C=CC=CC=1.C(OCC)(=O)C.CCCCCC.C(Cl)(Cl)Cl>[C:2]([O:5][CH2:6][CH:7]1[O:11][CH:10]([C:12]2[CH2:13][S:14][C@@H:15]3[C@H:31]([NH:32][C:33](=[O:41])[CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:30](=[O:42])[N:16]3[C:17]=2[C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([O:28][CH3:29])=[CH:24][CH:23]=2)=[O:19])[CH2:9][CH2:8]1)(=[O:4])[CH3:3]

Participants

8

Reactant 4

HCID 692673-Nitrobenzyl alcohol2×HCID 517045Sodium Acetate2×HCID 569933374-methoxybenzyl (6R,7R)-3-[(2S,5R)-5-acetoxymethyltetrahydrofuran-2-yl]-7-phenylacetamidoceph-3-em-4-carboxylateHCID 178527699HCID 178527699, compound

Product 1

HCID 542139684-Methoxybenzyl (6R,7R)-3-(5-acetoxymethyl-tetrahydrofuran-2-yl)-7-phenylacetamidoceph-3-em-4-carboxylate

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6212ChloroformSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

A solution of the phosphorane from Example 31(g) (517 mg) in dry toluene (100 ml) was heated at reflux under dry argon for 8 hours and evaporated. the residue was chromatographed on silica gel eluting with ethyl acetate/hexane mixtures to give two fractions. The less polar fraction contained 4-methoxybenzyl (6R, 7R) -3- [ (2S, 5R) -5-acetoxymethyltetrahydro-furan-2-yl]-7-phenylacetamidoceph-3-em-4-carboxylate, a foam (105 mg); νmax (CHCl3) 3410, 1784, 1726 and 1683 cm-1 ; δH (CDCl3) 1.53-1.83 (3 H, m), 2.09 (3 H, s), 2.19-2.36 (1 H, m), 3.30 and 3.55 (2 H, ABq, J 18.9 Hz), 3.60 and 3.69 (2 H, ABq, J 16.2 Hz), 3.81 (3 H, s), 4.01-4.21 (3 H, m), 4.90 (1 H, d, J 4.8 Hz), 4.96 (1 H, dd, J 8.3, 6.7 Hz), 5.12 and 5.17 (2 H, AA'q, J 12.5 Hz), 5.81 (1 H, dd, J 9.2, 4.8 Hz), 5.97 (1 H, d, J 9.2 Hz), 6.85-6.92 (2 H, m), 7.25-7.41 (7 H, m). (Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MH+ (581), MNa+ (603)]. The more polar fraction contained 4-methoxybenzyl (6R,7R)-3-[(2R,SS)-5-acetoxymethyl-tetrahydrofuran-2-yl]-7-phenylacetamidoceph-3-em-4-carboxylate, a solid (19lmg), m.p. 185-187° C. (needles ex ethyl acetate/hexane); νmax (CHC13) 3407, 1785, 1731 and 1682 cm-1 ; δH (CDCl3) 1.53-1.78 (2 H, m), 1.90-2.05 (2 H, m), 2.08 (3 H, s), 3.35 and 3.57 (2 H, ABq, 3 18.0 Hz), 3.61 and 3.69 (2 H, ABq, J 16.2 Hz), 3.80 (3 H, s), 4.01-4.19 (3 H, m), 4.91 (1 H, d, J 4.8 Hz), 5.12-5.27 (3 H, m), 5.74 (1 H, dd, J 4.8, 9.0 Hz), 6.04 (1 H, d, J 9.0 Hz), 6.85-6.91 (2 H, m), 7.25- 7.41 (7 H, m). (Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MH+ (581), MNa+ (603)].

Workup

  1. temperatureat reflux under dry argon for 8 hours
  2. customevaporated
  3. customthe residue was chromatographed on silica gel eluting with ethyl acetate/hexane
  4. customto give two fractions

Sources & evidence

ORD record
ord-cc00454694c24079832c849e31a3826a
Source dataset
uspto-grants-1999_12
Patent number
US06001997

Linked notes

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