Dicyclohexylcarbodiimide → HCID 178477372, compound

HRID 1679206

Reaction equation

HRID 1679206 reaction equation
[O:1]([N:8]=[C:9]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[C:10]([OH:12])=O)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[NH2:19][C@@H:20]1[C:51](=[O:52])[N:22]2[C:23]([C:35]([O:37][CH:38]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[C:39]3[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=3)=[O:36])=[C:24]([CH:27]([S:29][C:30]3[NH:34][N:33]=[N:32][N:31]=3)[CH3:28])[CH2:25][S:26][C@H:21]12.C1(N=C=NC2CCCCC2)CCCCC1>C(Cl)Cl>[CH3:28][CH:27]([S:29][C:30]1[NH:31][N:32]=[N:33][N:34]=1)[C:24]1[CH2:25][S:26][C@@H:21]2[C@H:20]([NH:19][C:10](=[O:12])[C:9](=[N:8][O:1][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)[C:51](=[O:52])[N:22]2[C:23]=1[C:35]([O:37][CH:38]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=1)=[O:36]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 538098242-Phenoxyimino-2-phenylacetic acidHCID 178477368HCID 178477368, compound

Product 1

HCID 178477372HCID 178477372, compoundYield 87%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A suspension of 2-phenoxyimino-2-phenylacetic acid (464mg) in dry methylene dichloride (25ml) was added, over 5 minutes, to a stirred solution of diphenylmethyl 7β-amino-3-(1-methyltetrazol-5-ylthiomethyl)-ceph-3-em-4-carboxylate (989mg) and dicyclohexylcarbodiimide (454mg) in methylene dichloride (25ml). After stirring for a further 2 hours, the solvent was evaporated in vacuo; the residue was suspended in ethyl acetate (60 ml), the insoluble material filtered off, and the filtrate washed with saturated sodium bicarbonate:water = 1:1, water, and brine (30 ml of each), dried, and evaporated to a foam (1.56g). A solution of this foam is benzene (10 ml) was purified by chromatography on kieselgel (60g), with benzene:ethyl acetate = 10:1 as eluant. Appropriate fractions were combined and evaporated to dryness in vacuo to give diphenylmethyl 3-(1-methyltetrazol-5-ylthiomethyl)-7β-[2-phenoxyimino-2 -phenylacetamido]-ceph-3-em-4-carboxylate (syn-isomer) as an orange foam (1.16g, 87%). A solution of this foam in a mixture of trifluoroacetic acid (4ml) and anisole (1ml) was kept at 23° for 5 minutes, and the solvents were removed at 40° (2mm). The residue was suspended in ether (80 ml), saturated sodium bicarbonate:water = 1:3 (120ml) was added, and the mixture was stirred until all the solid had dissolved (ca. 10 minutes). The aqueous phase was separated, covered with ethyl acetate (150 ml), and acidified to pH 2 with 2N-hydrochloric acid. The organic phase was separated, washed with water, and brine (50ml of each), and the solvent evaporated in vacuo. The residue was dissolved in acetone (50ml), the solution stirred for 5 minutes with charcoal (ca. 1g), and the mixture filtered through a pad of kieselguhr. The filtrate was dried and evaporated to a foam (780mg), which was dissolved in ethyl acetate, and the solution run into petroleum ether to give the title acid as a colourless, amorphous solid (640mg, 63.3%); [α]D23 - 64° (c 1.01, acetone); λmax. (0.1 M-pH 6 phosphate buffer) 261 nm. (ε 19,200); τ (DMSO-d6) values include -0.11 (NH, d, J 8 Hz.), 4.00 (7-H, dd, J 5 and 8 Hz.), 4.70 (6-H, d, J 5 Hz), and 6.04 (CH3 --).

Workup

  1. customthe solvent was evaporated in vacuo
  2. filtrationthe insoluble material filtered off
  3. washthe filtrate washed with saturated sodium bicarbonate
  4. dry with materialwater = 1:1, water, and brine (30 ml of each), dried
  5. customevaporated to a foam (1.56g)
  6. customwas purified by chromatography on kieselgel (60g), with benzene
  7. customevaporated to dryness in vacuo

Sources & evidence

ORD record
ord-f3a79723845e49e5a5bcf840c7799b8b
Source dataset
uspto-grants-1978_03
Patent number
US04079178

Linked notes

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