Phosphorus oxychloride → 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 325394Notes

Reaction equation

P(Cl)(Cl)(Cl)=O.[O:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH:7]1[O:12][CH:13]([C:17]1[N:18]=[C:19]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])[S:20][CH:21]=1)[C:14]([OH:16])=O.[CH3:27][N:28]1[C:32]([S:33][CH2:34][C:35]2[CH2:36][S:37][C@@H:38]3[CH:45]([NH2:46])[C:44](=[O:47])[N:39]3[C:40]=2[C:41]([OH:43])=[O:42])=[N:31][N:30]=[N:29]1.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.C(=O)(O)[O-].[Na+]>C(OCC)(=O)C.CN(C)C=O>[CH3:27][N:28]1[C:32]([S:33][CH2:34][C:35]2[CH2:36][S:37][C@@H:38]3[CH:45]([NH:46][C:14](=[O:16])[CH:13]([O:12][CH:7]4[CH2:8][CH2:9][CH2:10][CH2:11][O:6]4)[C:17]4[N:18]=[C:19]([NH:22][S:23]([CH3:26])(=[O:25])=[O:24])[S:20][CH:21]=4)[C:44](=[O:47])[N:39]3[C:40]=2[C:41]([OH:43])=[O:42])=[N:31][N:30]=[N:29]1

Participants

Conditions

Temperature: -20 °C

Procedure

To dimethylformamide (0.12 g.) was dropwise added phosphorus oxychloride (0.29 g.) under stirring and ice-cooling, and the mixture was stirred for 30 minutes at 40° C. and then cooled to -20° C. To the mixture was added all at once a solution of 2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetic acid, which can be represented as 2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro-1,3-thiazol-4-yl)acetic acid, (0.52 g.) in ethyl acetate (7 ml.) at -20° C. with stirring, and then the mixture was stirred for 30 minutes at -20° to -10° C. Thus obtained mixture was added all at once to the solution prepared in the similar manner as in Example 1 from 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-amino-3-cephem-4-carboxylic acid (0.51 g.), bis(trimethylsilyl)acetamide (1.5 ml.) and ethyl acetate (10 ml.), at -40° C. The mixture was stirred for 30 minutes at the same temperature and further stirred for 1.5 hours at -20° to -10° C. After the reaction, the reaction mixture was poured into 5% sodium bicarbonate aqueous solution (20 ml.). The mixture was washed with ethyl acetate, and the aqueous layer was separated therefrom. Thus obtained aqueous layer was post-treated in a similar manner at that of example 5 to give 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be prevented as 3-(1-methyl-1H-tetrazol-5-yl)thiomethyl-7-[2-(2-tetrahydropyranyl)oxy-2-(2-mesylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (0.41 g.)

Workup

temperatureice-cooling
stirringthe mixture was stirred for 30 minutes at 40° C.
stirringwith stirring
stirringthe mixture was stirred for 30 minutes at -20° to -10° C
additionThus obtained mixture was added all at once to the solution
stirringThe mixture was stirred for 30 minutes at the same temperature
stirringfurther stirred for 1.5 hours at -20° to -10° C
customAfter the reaction
washThe mixture was washed with ethyl acetate
customthe aqueous layer was separated
additionThus obtained aqueous layer was post-treated in a similar manner at that of example 5

Sources & evidence

ORD record: ord-7d1815508af6440a98a0cc05fdbc7810
Source dataset: uspto-grants-1984_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US04440766

Reaction notes

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