Sodium Hydroxide → 3-(5-Methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

HRID 638449Notes

Reaction equation

HRID 638449 reaction equation
[CH3:1][C:2]1[S:6][C:5]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:38])[C:22]([C:24]4[NH:25][C:26](=[N:29][C:30]([O:32][C:33]([CH2:36][CH3:37])([CH3:35])[CH3:34])=[O:31])[S:27][CH:28]=4)=[O:23])[C:18](=[O:39])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:4][N:3]=1.[OH-].[Na+].[BH4-].[Na+]>CO.O>[CH3:1][C:2]1[S:6][C:5]([S:7][CH2:8][C:9]2[CH2:10][S:11][C@@H:12]3[CH:19]([NH:20][C:21](=[O:38])[CH:22]([OH:23])[C:24]4[N:25]=[C:26]([NH:29][C:30]([O:32][C:33]([CH2:36][CH3:37])([CH3:34])[CH3:35])=[O:31])[S:27][CH:28]=4)[C:18](=[O:39])[N:13]3[C:14]=2[C:15]([OH:17])=[O:16])=[N:4][N:3]=1

Participants

6

Reactant 3

HCID 14798Sodium HydroxideHCID 4311764Sodium borohydrideHCID 178447168HCID 178447168, compound

Product 1

HCID 704906533-(5-Methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

To a solution of 3-(5-methyl-1,3,4-thiadiazol-2-yl)-thiomethyl-7-[2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)-glyoxylamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-(2-tert-pentyloxycarbonylimino-2,3-dihydro-1,3-thiazol-4-yl)glyoxylamido]-3-cephem-4-carboxylic acid, (3.36 g.) in methanol (35 ml.) was added 1N sodium hydroxide aqueous solution (5.5 ml.) under ice-cooling, and to the mixture was dropwise added an aqueous solution of sodium borohydride (91 mg.) in water (2.5 ml.) over 2 minutes at 10° to 15° C. The mixture was stirred for 10 minutes at the same temperature, and the methanol was distilled off from the mixture below 40° C. under reduced pressure. The remaining aqueous solution was washed with a small amount of ethyl acetate, adjusted to pH 5 to 6, with 10% hydrochloric acid, further washed with a small amount of ethyl acetate. The solution was adjusted to pH 2 with 10% hydrochloric acid, and then extracted with ethyl acetate. The extract was washed with water and a saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate and then treated with an activated charcoal. The solvent was distilled off from the extract till the volume of the extract became a smaller amount. The precipitates were collected by filtration, washed with a small amount of ethyl acetate, and then dried to give 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylamino-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, which can be represented as 3-(5-methyl-1,3,4-thiadiazol-2-yl)thiomethyl-7-[2-hydroxy-2-(2-tert-pentyloxycarbonylimino-2,3-dihydro-1,3-thiazol-4-yl)acetamido]-3-cephem-4-carboxylic acid, (1.69 g.). On the other hand, the mother liquor and the ethyl acetate washing were combined together and concentrated under reduced pressure, and then the precipitates were similarly treated as aforementioned to give the same object compound (0.80 g.).

Workup

  1. temperaturecooling
  2. distillationthe methanol was distilled off from the mixture below 40° C. under reduced pressure
  3. washThe remaining aqueous solution was washed with a small amount of ethyl acetate
  4. washfurther washed with a small amount of ethyl acetate
  5. extractionextracted with ethyl acetate
  6. washThe extract was washed with water
  7. dry with materiala saturated aqueous solution of sodium chloride in turn, dried over magnesium sulfate
  8. additiontreated with an activated charcoal
  9. distillationThe solvent was distilled off from the
  10. extractionextract till the volume of the extract
  11. filtrationThe precipitates were collected by filtration
  12. washwashed with a small amount of ethyl acetate
  13. customdried

Sources & evidence

ORD record
ord-2dedb115f5a544a7bb23a28ce063338a
Source dataset
uspto-grants-1985_12
Patent number
US04560765

Reaction notes

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