Phosphorus pentachloride → benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 1153923노트

반응식

HRID 1153923 반응식
[NH2:1][CH:2]1[C:27](=[O:28])[N:4]2[C:5]([C:11]([O:13][CH:14]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:15]3[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=3)=[O:12])=[C:6]([CH2:9][Cl:10])[CH2:7][S:8][C@H:3]12.C[Si](C([Si](C)(C)C)C(N)=O)(C)C.[CH3:41][O:42]/[N:43]=[C:44](/[C:48]1[N:49]=[C:50]([NH:53][C:54]([C:67]2[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=2)([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[C:55]2[CH:60]=[CH:59][CH:58]=[CH:57][CH:56]=2)[S:51][CH:52]=1)\[C:45](O)=[O:46].P(Cl)(Cl)(Cl)(Cl)Cl>CC#N.C(Cl)Cl.O>[Cl:10][CH2:9][C:6]1[CH2:7][S:8][C@@H:3]2[CH:2]([NH:1][C:45](=[O:46])/[C:44](=[N:43]\[O:42][CH3:41])/[C:48]3[N:49]=[C:50]([NH:53][C:54]([C:61]4[CH:62]=[CH:63][CH:64]=[CH:65][CH:66]=4)([C:67]4[CH:72]=[CH:71][CH:70]=[CH:69][CH:68]=4)[C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][CH:60]=4)[S:51][CH:52]=3)[C:27](=[O:28])[N:4]2[C:5]=1[C:11]([O:13][CH:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1)=[O:12]

참가 물질

8

반응물 4

HCID 24819Phosphorus pentachlorideHCID 5928144(Z)-2-methoxymino-2-(2-(tritylamino)thiazol-4-yl)acetic acidHCID 11708267BistrimethylsilylacetamidHCID 13239626Benzhydryl 7-Amino-3-chloromethyl-3-cephem-4-carboxylate

생성물 1

HCID 13239631benzhydryl (6R)-3-(chloromethyl)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

시약·촉매·용매 3

HCID 962Water용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

실험 절차

Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate prepared in Preparation No. 4 (2.29 g, 5.52 mmoles) in CH3CN (57 mL) was treated with bis(trimethylsilyl)acetamide (BSA, 4.09 mL, 16.6 mmoles) at room temperature for 50 minutes to give a clear solution. To the solution was added an acid chloride solution, which was prepared from (Z)-2-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid (IV-1) (2.04 g, 4.60 mmoles) and PCl5 (1.15 g, 5.52 mmoles) in methylene chloride (20 mL). The mixture was stirred at room temperature for 30 minutes, poured into cold water (200 mL) and extracted with ethyl acetate (3×100 mL). The combined extracts were washed with aqueous NaCl, dried and evaporated. The residual syrup (4 g) was chromatographed on a silica gel (150 g) column by eluting with 10:1 and 3:1 mixtures of toluene and ethyl acetate successively. The fractions containing the desired compound were combined and evaporated to afford 2.61 g (68%) of VI-1 as an amorphous powder.

후처리

  1. customto give a clear solution
  2. extractionextracted with ethyl acetate (3×100 mL)
  3. washThe combined extracts were washed with aqueous NaCl
  4. customdried
  5. customevaporated
  6. customThe residual syrup (4 g) was chromatographed on a silica gel (150 g) column
  7. washby eluting with 10:1 and 3:1 mixtures of toluene and ethyl acetate successively
  8. additionThe fractions containing the desired compound
  9. customevaporated
  10. customto afford 2.61 g (68%) of VI-1 as an amorphous powder

출처 및 근거

ORD 기록
ord-6bdf289397904421a942736b16186ff1
출처 데이터셋
uspto-grants-1984_12
특허 번호
US04486586

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