Dichloromethane → HCID 54407251, compound

HRID 1649272Notes

Reaction equation

HRID 1649272 reaction equation
[CH:1]([O:14][C:15]([C:17]1[N:18]2[CH:21]([S:22][CH2:23][C:24]=1[CH2:25]C=O)[CH:20]([NH:28][C:29](=[O:59])[C:30](=[N:56][O:57][CH3:58])[C:31]1[N:32]=[C:33]([NH:36][C:37]([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)[C:38]3[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=3)[S:34][CH:35]=1)[C:19]2=[O:60])=[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.ClCl.P(OC1C=CC=CC=1)(OC1C=CC=CC=1)OC1C=CC=CC=1.[CH2:85]([Cl:87])[Cl:86]>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[CH2:25][CH:85]([Cl:87])[Cl:86])[CH:20]([NH:28][C:29](=[O:59])[C:30](=[N:56][O:57][CH3:58])[C:31]1[N:32]=[C:33]([NH:36][C:37]([C:44]3[CH:49]=[CH:48][CH:47]=[CH:46][CH:45]=3)([C:50]3[CH:55]=[CH:54][CH:53]=[CH:52][CH:51]=3)[C:38]3[CH:39]=[CH:40][CH:41]=[CH:42][CH:43]=3)[S:34][CH:35]=1)[C:19]2=[O:60])=[O:16])([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 6344Dichloromethane2×HCID 7540Triphenyl phosphiteHCID 24526ChlorineHCID 54340320HCID 54340320, compound2×

Product 1

HCID 54407251HCID 54407251, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

Following the procedure described in Example 11B, a solution of the syn isomer of 2-benzhydryloxycarbonyl-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-3-(2-oxoethyl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene (product 13c) (2.3 g) in methylene chloride (15 cc), cooled to -40° C., is treated with a 0.5 M solution (5.5 cc), in methylene chloride, of the addition compound of chlorine and triphenyl phosphite. The reaction mixture is stirred for 3 hours at a temperature between -40° C. and -20° C. and then diluted with ethyl acetate (200 cc). The organic solution is decanted and washed with a semisaturated solution of sodium bicarbonate and sodium chloride (50 cc) and then a saturated solution of sodium chloride (3×50 cc). The aqueous phases are reextracted with ethyl acetate (50 cc) and the combined organic solutions are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. The residue is stirred with isopropyl ether (150 cc) for 16 hours. The precipitate is filtered off, washed with isopropyl ether (50 cc) and then redissolved in methylene chloride (50 cc) and fixed to silica gel (0.2-0.06) (8 g), which is deposited on a column of silica gel (0.06-0.04) (diameter of the column: 1.8 cm; height: 35 cm). Elution is carried out with a mixture of cyclohexane and ethyl acetate (75/25 by volume) under a pressure of 80 kPa, 50 cc fractions being collected. Fractions 5 to 7, containing the pure product, are combined and concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C. This yields the syn isomer of 2-benzhydryloxycarbonyl-3-(2,2-dichloroethyl)-7-[2-methoxyimino-2-(2-tritylaminothiazol-4-yl)-acetamido]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene (product 13d) (0.25 g) in the form of a whitish solid.

Workup

  1. customThe organic solution is decanted
  2. washwashed with a semisaturated solution of sodium bicarbonate and sodium chloride (50 cc)
  3. concentrationthe combined organic solutions are concentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C
  4. stirringThe residue is stirred with isopropyl ether (150 cc) for 16 hours
  5. filtrationThe precipitate is filtered off
  6. washwashed with isopropyl ether (50 cc)
  7. dissolutionredissolved in methylene chloride (50 cc)
  8. washElution
  9. additionis carried out with a mixture of cyclohexane and ethyl acetate (75/25 by volume) under a pressure of 80 kPa, 50 cc fractions
  10. custombeing collected
  11. additionFractions 5 to 7, containing the pure product
  12. concentrationconcentrated to dryness under reduced pressure (30 mm Hg; 4 kPa) at 30° C

Sources & evidence

ORD record
ord-6b79f46ffe2b40ecba63043fa5db309b
Source dataset
uspto-grants-1983_11
Patent number
US04415562

Reaction notes

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