4-Hydroxymethylpyridine → (4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(pyridin-4-ylmethoxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 728751Notes

Reaction equation

HRID 728751 reaction equation
[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:52]/[O:53][CH3:54])/[C:27]([NH:29][C@@H:30]2[C:50](=[O:51])[N:32]3[C:33]([C:38]([O:40][CH2:41][C:42]4[CH:47]=[CH:46][C:45]([O:48][CH3:49])=[CH:44][CH:43]=4)=[O:39])=[C:34]([OH:37])[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:74]1[CH:79]=[CH:78][C:77]([CH2:80]O)=[CH:76][CH:75]=1.CCOC(/N=N/C(OCC)=O)=O>O1CCCC1>[C:1]([NH:20][C:21]1[S:22][CH:23]=[C:24](/[C:26](=[N:52]/[O:53][CH3:54])/[C:27]([NH:29][C@@H:30]2[C:50](=[O:51])[N:32]3[C:33]([C:38]([O:40][CH2:41][C:42]4[CH:43]=[CH:44][C:45]([O:48][CH3:49])=[CH:46][CH:47]=4)=[O:39])=[C:34]([O:37][CH2:80][C:77]4[CH:78]=[CH:79][N:74]=[CH:75][CH:76]=4)[CH2:35][S:36][C@H:31]23)=[O:28])[N:25]=1)([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

6

Reactant 4

HCID 114724-HydroxymethylpyridineHCID 11776TriphenylphosphineHCID 5462977Diethyl azodicarboxylateHCID 139740822(4-methoxyphenyl)methyl (6R,7R)-3-hydroxy-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

Product 1

HCID 14672344(4-methoxyphenyl)methyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(pyridin-4-ylmethoxy)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylateYield 56.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

2.29 g (3.01 mmol) of p-methoxybenzyl 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-hydroxy-3-cephem-4-carboxylate and 982 mg (3.75 mmol) of triphenylphosphine were dissolved in 48 ml of tetrahydrofuran, and a solution of 408 mg (3.74 mmol) of 4-pyridinemethanol in 24 ml of tetrahydrofuran was added thereto at room temperature under nitrogen atmosphere. Then, a solution of 0.58 ml (3.67 mmol) of diethylazodicarboxylate in 24 ml of tetrahydrofuran was dropwise added thereto at room temperature, and the mixture was stirred for 2 hours at the same temperature. The solvent was distilled off. The residue was dissolved in ethyl acetate, washed sequentially with water, a saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution and dried over magnesium sulfate. The solvent was distilled off and the residue was purified by silica gel column chromatography (Wakogel C-300, elution with 1% methanol-chloroform) to obtain 1.46 g (yield: 56.9%) of p-methoxybenzyl 7β-[2-(2-tritylaminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-(4-pyridylmethoxy)-3-cephem-4-carboxylate as a light yellow powder. 660 mg (0.774 mmol) of this powder was dissolved in 4.1 ml of dichloromethane and 0.9 ml of anisole, and 6.6 ml of trifluoroacetic acid was dropwise added thereto under cooling with ice. The mixture was stirred for 1 hour at the same temperature. The solvent was distilled off, and isopropyl ether was added to the residue to obtain the trifluoroacetate of the above-identified compound as a powder. This trifluoroacetate was dissolved in water and adjusted to pH6.5 with a sodium hydrogencarbonate aqueous solution. The solution was purified by reversed phase column chromatography (Chemco LC-SORB, SP-B-ODS, elution with 20% methanol aqueous solution) and freeze-dried to obtain 221 mg (yield: 55.7%) of the above-identified compound.

Workup

  1. customat room temperature
  2. distillationThe solvent was distilled off
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed sequentially with water
  5. dry with materiala saturated sodium hydrogencarbonate aqueous solution and a saturated sodium chloride aqueous solution and dried over magnesium sulfate
  6. distillationThe solvent was distilled off
  7. customthe residue was purified by silica gel column chromatography (Wakogel C-300, elution with 1% methanol-chloroform)

Sources & evidence

ORD record
ord-bdf7ef9273c64811ab589e3514b76e77
Source dataset
uspto-grants-1991_09
Patent number
US05049665

Reaction notes

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