Dicyclohexylcarbodiimide → 4-Methoxybenzyl (6R,7R)-7-[(R)-2-t-butoxycarbonylamino-2-(4-hydroxyphenyl)acetamido]-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

HRID 376592Notes

Reaction equation

HRID 376592 reaction equation
[NH2:1][C@@H:2]1[C:26](=[O:27])[N:4]2[C:5]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)=[O:15])=[C:6]([C@H:9]3[CH2:13][CH2:12][CH2:11][O:10]3)[CH2:7][S:8][C@H:3]12.C1(N=C=NC2CCCCC2)CCCCC1.[C:43]([O:47][C:48]([NH:50][C@H:51]([C:55]1[CH:60]=[CH:59][C:58]([OH:61])=[CH:57][CH:56]=1)[C:52](O)=[O:53])=[O:49])([CH3:46])([CH3:45])[CH3:44]>C1COCC1>[C:43]([O:47][C:48]([NH:50][C@H:51]([C:55]1[CH:60]=[CH:59][C:58]([OH:61])=[CH:57][CH:56]=1)[C:52]([NH:1][C@@H:2]1[C:26](=[O:27])[N:4]2[C:5]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=3)=[O:15])=[C:6]([C@H:9]3[CH2:13][CH2:12][CH2:11][O:10]3)[CH2:7][S:8][C@H:3]12)=[O:53])=[O:49])([CH3:46])([CH3:44])[CH3:45]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 11821572Boc-4-hydroxy-D-phenylglycineHCID 538410274-Methoxybenzyl (6R,7R)-7-Amino-3-((R)-tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate

Product 1

HCID 545444554-Methoxybenzyl (6R,7R)-7-[(R)-2-t-butoxycarbonylamino-2-(4-hydroxyphenyl)acetamido]-3-[(R)-tetrahydrofuran-2-yl]ceph-3-em-4-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

4-Methoxybenzyl (6R,7R)-7-amino-3-[(R)-tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate (136mg, 0.35mmol) [See example 6] in THF (10ml) was stirred in an ice bath with dicyclohexylcarbodiimide (108mg, 0.52mmol) then (R)-2-t-butoxycarbonylamino-2-(4-hydroxyphenyl)acetic acid (139mg, 0.52mmol) in THF (3ml) was added dropwise over 2 min. The mixture was stirred at 0° C. for 30 min then at room temperature for 30 min. It was filtered and evaporated and the residue chromatographed on silica gel eluting with ethyl acetate/hexane mixtures. The title compound was obtained as a white solid (212mg, 95%); δH (CDCl3) 1.10-2.0 (4H,m), 1.42 (9H,s), 3.18 and 3.43 (2H,ABq, J 17Hz), 3.80 (3H,s), 3.77-3.88 (2H,m), 4.89 (1H,d, J 5Hz), 5.10 (1H,t, J 7Hz), 5.11 (1H,d, J 5Hz), 5.19 (2H, s), 5.65 (1H,d, J 5Hz exch), 5.69 (1H,dd, J 4,9Hz), 6.72 (2H,d, J 8Hz), 6.81 (1H,d, J 9Hz exch), 6.88 (2H,d, J 9Hz), 7.10 (2H,d, J 8Hz) and 7.33 (2H,d,J 9Hz). (Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (938)].

Workup

  1. waitat room temperature for 30 min
  2. filtrationIt was filtered
  3. customevaporated
  4. customthe residue chromatographed on silica gel eluting with ethyl acetate/hexane mixtures

Sources & evidence

ORD record
ord-1286ce9b392e4665b6ff6e1a04ddfe38
Source dataset
uspto-grants-2000_02
Patent number
US06020329

Reaction notes

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