Hydrochloric Acid → (αZ)-2-Amino-α-[(2-methoxy-2-oxoethoxy)imino]-4-thiazoleacetic acid

HRID 646533Notes

Reaction equation

HRID 646533 reaction equation
C([O-])(=O)C.[Na+].[NH2:6][C:7]([NH2:9])=[S:8].Cl[CH2:11][C:12](=O)/[C:13](=[N:17]/[O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])/[C:14]([OH:16])=[O:15].Cl>O>[NH2:6][C:7]1[S:8][CH:11]=[C:12](/[C:13](=[N:17]/[O:18][CH2:19][C:20]([O:22][CH3:23])=[O:21])/[C:14]([OH:16])=[O:15])[N:9]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 517045Sodium AcetateHCID 2723790ThioureaHCID 109006694-Chloro-2-[(Z)-(methoxycarbonyl)methoxyimino]-3-oxobutyric acid

Product 1

HCID 12108608(αZ)-2-Amino-α-[(2-methoxy-2-oxoethoxy)imino]-4-thiazoleacetic acidYield 87.1%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
12 °C

Procedure

Sodium acetate (120 gm) is added to water (400 ml) and thiourea (41.6 gm) at 25-30° C., cooled to 12° C. and then (Z)-4-chloro-2-[[(methoxycarbonyl)methoxy]imino]acetoacetic acid (100 gm) Is added at 12° C. The contents are stirred for 3 hours at 25-30° C., cooled to 5° C., pH is adjusted to 3.0 with conc. hydrochloric acid at 5-0° C. Then the reaction mass is cooled to 0° C. and stirred for 1 hour at 0-5° C. The resulting solid is filtered, washed two times with chilled water (each time 100 ml) and dried at 100-105° C. to give 95 gm of (Z)-2-(2-aminothiazol-4-yl)-(methoxycarbonyl)methoxyimino acetic acid (High Performance Liquid Chromatographic (HPLC) purity: 99.5%). B) 2,2′-Dithiobis(benzothiazole) (117.75 gm) and acetonitrile (580 ml) are added to (Z)-2-(2-aminothiazol-4-yl)-(methoxycarbonyl)methoxyimino acetic acid (75 gm) at 25-30° C. and then distilled off 50 ml of acetonitrile under vacuum at 45-50° C. The contents are cooled to 25° C. under N2 atmosphere, flushed with 20 ml of acetonitrile and cooled to 13° C. Triethylamine (30 gm) is added to the contents at 13° C., stirred for 30 minutes at 13° C. under N2 atmosphere and then cooled to 0° C. Triphenylphosphine (96 gm) is added to the reaction mass at 0° C., stirred for 1 hour at 0-2° C. and cooled to −10° C. Then the reaction mass is stirred for 4 to 5 hours at −10° C., filtered the mass and washed with chilled methanol. Methanol (470 ml) is added to the reaction mass at 25° C., cooled to −5° C. under N2 atmosphere, the wet cake is added for 5 minutes at −5° C. and stirred for 1 hour at −5° C. Filtered the mass, washed with methanol (100 ml) and dried to yield 93.75 gm of 2-mercapto-1,3-benzothiazolyl-(Z)-2-(2-aminothiazol-4-yl)-2-(methoxycarbonyl)-methoxyimino acetate (HPLC purity 98.2%).

Workup

  1. temperaturecooled to 5° C.
  2. temperatureThen the reaction mass is cooled to 0° C.
  3. stirringstirred for 1 hour at 0-5° C
  4. filtrationThe resulting solid is filtered
  5. washwashed two times with chilled water (each time 100 ml) and
  6. customdried at 100-105° C.

Sources & evidence

ORD record
ord-b2f34c13b53a423c8b7621075a11eb80
Source dataset
uspto-grants-2010_04
Patent number
US07705142B2

Reaction notes

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