Trifluoroacetic acid → HCID 13489017, compound

HRID 414856Notes

Reaction equation

HRID 414856 reaction equation
C([O:5][C:6]([NH:8][C@H:9]1[C@@H:12]([C:13](=[O:15])[NH2:14])[N:11]([O:16][CH2:17][C:18]([O:20][CH2:21][C:22]2[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][CH:23]=2)=[O:19])[C:10]1=[O:31])=O)(C)(C)C.C1(OC)C=CC=CC=1.FC(F)(F)C(O)=O.Cl.[Cl:48][CH2:49][C:50]([NH:52][C:53]1[S:54][CH:55]=[C:56](/[C:58](=[N:62]/[O:63][CH2:64][C:65]([O:67][CH2:68][C:69]2[CH:74]=[CH:73][C:72]([N+:75]([O-:77])=[O:76])=[CH:71][CH:70]=2)=[O:66])/C(Cl)=O)[N:57]=1)=[O:51]>ClCCl.C(N(CC)CC)C.C1(C)C=CC=CC=1>[C:13]([C@H:12]1[N:11]([O:16][CH2:17][C:18]([O:20][CH2:21][C:22]2[CH:23]=[CH:24][C:25]([N+:28]([O-:30])=[O:29])=[CH:26][CH:27]=2)=[O:19])[C:10](=[O:31])[C@H:9]1[NH:8][C:6](=[O:5])/[C:58](/[C:56]1[N:57]=[C:53]([NH:52][C:50](=[O:51])[CH2:49][Cl:48])[S:54][CH:55]=1)=[N:62]\[O:63][CH2:64][C:65]([O:67][CH2:68][C:69]1[CH:74]=[CH:73][C:72]([N+:75]([O-:77])=[O:76])=[CH:71][CH:70]=1)=[O:66])(=[O:15])[NH2:14]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 7519AnisoleHCID 13470798HCID 13470798, compoundHCID 57133416HCID 57133416, compound

Product 1

HCID 13489017HCID 13489017, compoundYield 87%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×HCID 8471TriethylamineSolvent

Procedure

In 20 ml of dichloromethane is suspended 550 mg of (3S,4S)-3-(tert-butoxycarbonylamino)-4-carbamoyl-1-(p-nitrobenzyloxycarbonylmethoxy)-2-azetidinone, and 2 ml of anisole and 10 mL of trifluoroacetic acid are added to the suspension under ice-cooling with stirring. After the stirring under ice-cooling for 2 hours, 20 ml of toluene is added to the reaction solution, and the mixtuere is concentreated under reduced pressure. 20 ml of dichloromethane is added to the residue, and 1.06 ml of triethylamine and 964 mg of 2-(2-chloroacetamidothiazol-4-yl)-(Z)- 2-(p-nitrobenzyloxycarbonylmethoxyimino)acetyl chloride hydrochloride (prepared by the method as described in the Japanese Unexamined Patent Publication No. 131758/1982) are added, followed by stirring under ice-cooling for 2 hours. The solvent is distilled off under reduced pressure, and 15 ml of tetrahydrofuran and 15 ml of water are added to the residue. The mixture is adjusted to pH 7 with aqueous sodium hydrogen carbonate solution, and stirred under ice-cooling for 1 hour. The tetrahydrofuran is distilled off under reduced pressure, and crystals which separate out are recovered by filtration, and washed with aqueous sodium hydrogen carbonate solution, water, ether, ethyl acetate andeether successively to give 848 mg (83.0%) of (3S,4S)-4-carbamoyl-3-[2-(2-chloroacetamidothiazol-4-yl)-(Z)-2-(p-nitrobenzyloxycarbonylmethoxyimino)acetamido]-1-(p-nitrobenzyloxycarbonylmethoxy)-2-azetidinone as yellow crystals, which is shown by TLC to contain a slight amount of impurities but used as crude crystals in the substituent reaction, m.p. 147°-153° C.

Workup

  1. additionare added to the suspension under ice-
  2. temperaturecooling
  3. temperatureAfter the stirring under ice-cooling for 2 hours
  4. customprepared by the method
  5. addition131758/1982) are added
  6. stirringby stirring under ice-
  7. temperaturecooling for 2 hours
  8. distillationThe solvent is distilled off under reduced pressure, and 15 ml of tetrahydrofuran and 15 ml of water
  9. additionare added to the residue
  10. stirringstirred under ice-
  11. temperaturecooling for 1 hour
  12. distillationThe tetrahydrofuran is distilled off under reduced pressure, and crystals which
  13. customseparate out
  14. filtrationare recovered by filtration
  15. washwashed with aqueous sodium hydrogen carbonate solution, water, ether, ethyl acetate andeether successively

Sources & evidence

ORD record
ord-840e650e0d9744b889f968236bae928d
Source dataset
uspto-grants-1988_12
Patent number
US04794108

Reaction notes

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