N,N-Dimethylaniline → HCID 178514118, compound

HRID 638319Notes

Reaction equation

HRID 638319 reaction equation
C(Cl)(=O)C(Cl)=O.[CH:7]1([CH2:10][O:11]/[N:12]=[C:13](/[C:17]2[N:18]=[C:19]([NH:22][C:23]([C:36]3[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=3)([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[S:20][CH:21]=2)\[C:14]([OH:16])=O)[CH2:9][CH2:8]1.[NH2:42][C@@H:43]1[C:71](=[O:72])[N:45]2[C:46]([C:55]([O:57][CH:58]([C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)[C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=3)=[O:56])=[C:47]([CH2:50][O:51][C:52](=[O:54])[NH2:53])[CH2:48][S:49][C@H:44]12.CN(C)C1C=CC=CC=1>C(Cl)Cl.CN(C)C=O>[C:52]([O:51][CH2:50][C:47]1[CH2:48][S:49][C@@H:44]2[C@H:43]([NH:42][C:14](=[O:16])/[C:13](=[N:12]\[O:11][CH2:10][CH:7]3[CH2:8][CH2:9]3)/[C:17]3[N:18]=[C:19]([NH:22][C:23]([C:30]4[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=4)([C:36]4[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=4)[C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[S:20][CH:21]=3)[C:71](=[O:72])[N:45]2[C:46]=1[C:55]([O:57][CH:58]([C:59]1[CH:64]=[CH:63][CH:62]=[CH:61][CH:60]=1)[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1)=[O:56])(=[O:54])[NH2:53]

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 65578Oxalyl chlorideHCID 13127403HCID 13127403, compoundHCID 13269246HCID 13269246, compound

Product 1

HCID 178514118HCID 178514118, compoundYield 83.6%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (0.37 ml) was added to a solution of N,N-dimethylformamide (0.38 ml) in methylene chloride (10 ml) at -20° with stirring. After five minutes at 0°, the mixture was recooled to -20° and (Z)-2-cyclopropylmethoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid (1.94 g) was added. The solution was stirred at 0° for ten minutes before recooling to -20°. A slurry of diphenylmethyl (6R,7R)-7-amino-3-carbamoyloxymethylceph-3-em-4-carboxylate (1.76 g) in methylene chloride (10 ml) containing N,N-dimethylaniline (1.26 ml) was added. The solution was allowed to warm to 21° and was stirred for 1.5 hours. After dilution with methylene chloride, the solution was washed with dilute hydrochloric acid and water, each time back-extracting with methylene chloride. The combined organic layers were dried (magnesium sulphate) and concentrated. The solution was loaded into a column of Sorbsil U30 (70 g) which was eluted with a gradient of ethyl acetate (10 to 100%) in petroleum ether (b.p. 40°-60°). Evaporation of the appropriate eluate gave the title compound (3.03 g) as a foam, [α]D21 +10.7° (c 1.03, CHCl3); νinfl 238.5 nm (E1 cm1% 2.78), 258.5 (E1 cm1% 227), 264.5 (E1 cm1% 212), 271.5 (E1 cm1% 186) and 296.5 (E1 cm1% 88)

Workup

  1. customwas recooled to -20°
  2. stirringThe solution was stirred at 0° for ten minutes
  3. custombefore recooling to -20°
  4. additionwas added
  5. temperatureto warm to 21°
  6. stirringwas stirred for 1.5 hours
  7. washAfter dilution with methylene chloride, the solution was washed with dilute hydrochloric acid and water
  8. extractioneach time back-extracting with methylene chloride
  9. dry with materialThe combined organic layers were dried (magnesium sulphate)
  10. concentrationconcentrated
  11. wash(70 g) which was eluted with a gradient of ethyl acetate (10 to 100%) in petroleum ether (b.p. 40°-60°)
  12. customEvaporation of the appropriate eluate

Sources & evidence

ORD record
ord-facf66d2b47d4fdcb99e7296c1b12775
Source dataset
uspto-grants-1985_12
Patent number
US04560683

Reaction notes

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