Phosphorus trichloride → 2-Benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene

HRID 463581Notes

Reaction equation

HRID 463581 reaction equation
[CH:1]([O:14][C:15]([C:17]1[N:18]2[CH:21]([S:22](=O)[CH2:23][C:24]=1[CH:25]=[C:26]([S:28][C:29]1[S:33][C:32]([CH3:34])=[N:31][N:30]=1)[CH3:27])[CH:20]([NH:36][C:37](=[O:67])[C:38](=[N:64][O:65][CH3:66])[C:39]1[N:40]=[C:41]([NH:44][C:45]([C:58]3[CH:63]=[CH:62][CH:61]=[CH:60][CH:59]=3)([C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)[S:42][CH:43]=1)[C:19]2=[O:68])=[O:16])([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.CN(C)C(=O)C.P(Cl)(Cl)Cl.C(=O)(O)[O-].[Na+]>C(Cl)Cl.O.C(OCC)(=O)C>[CH:1]([O:14][C:15]([C:17]1[N:18]2[CH:21]([S:22][CH2:23][C:24]=1[CH:25]=[C:26]([S:28][C:29]1[S:33][C:32]([CH3:34])=[N:31][N:30]=1)[CH3:27])[CH:20]([NH:36][C:37](=[O:67])[C:38](=[N:64][O:65][CH3:66])[C:39]1[N:40]=[C:41]([NH:44][C:45]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=3)([C:52]3[CH:53]=[CH:54][CH:55]=[CH:56][CH:57]=3)[C:58]3[CH:59]=[CH:60][CH:61]=[CH:62][CH:63]=3)[S:42][CH:43]=1)[C:19]2=[O:68])=[O:16])([C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

8

Reactant 4

HCID 24387Phosphorus trichlorideHCID 31374DimethylacetamideHCID 516892Sodium BicarbonateHCID 544407692-Benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide

Product 1

HCID 536585572-Benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-eneYield 31.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
-10 °C

Procedure

A solution of the Z form of the syn isomer of 2-benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-5-oxide (2.52 g) in methylene chloride (40 cc) is cooled to -10° C. N,N-Dimethylacetamide (0.95 cc) and phosphorus trichloride (0.7 g) are added successively. The solution is stirred for 20 minutes at -10° C. and then poured into a saturated aqueous solution of sodium bicarbonate (50 cc). It is diluted with distilled water (200 cc) and extraction is carried out with ethyl acetate (300 cc). The organic phase is dried over sodium sulphate and concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. The residue is chromatographed on a column of Merck silica gel (0.06-0.20) (25 g) (diameter of the column: 2 cm; height: 15 cm). Elution is carried out with a 50/50 (by volume) ethyl acetate/cyclohexane mixture (500 cc), 30 cc fractions being collected. Fractions 4 to 13 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C. This yields the Z form of the syn isomer of 2-benzhydryloxycarbonyl-3-{2-[(2-methyl-1,3,4-thiadiazol-5-yl)-thio]-prop-1-en-1-yl}-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (0.77 g) in the form of a hard white foam.

Workup

  1. dry with materialThe organic phase is dried over sodium sulphate
  2. concentrationconcentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C
  3. customThe residue is chromatographed on a column of Merck silica gel (0.06-0.20) (25 g) (diameter of the column
  4. washElution
  5. custombeing collected
  6. concentrationFractions 4 to 13 are concentrated to dryness under reduced pressure (20 mm Hg; 2.7 kPa) at 20° C

Sources & evidence

ORD record
ord-e2660ce8f61d43fca5b95acb71323d09
Source dataset
uspto-grants-1985_05
Patent number
US04520193

Reaction notes

Loading…