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 1248767

反応式

HRID 1248767 の反応式
[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]

参加物

8

反応物 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

生成物 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

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6342Acetonitrile溶媒HCID 6344Dichloromethane溶媒

実験手順

Benzhydryl 7-amino-3-chloromethyl-3-cephem-4-carboxylate (V) 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-a) (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 VIa as an amorphous powder.

後処理

  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 VIa as an amorphous powder

出典と根拠

ORDレコード
ord-899aa6862b24476eb2d886578c711cd2
出典データセット
uspto-grants-1985_06
特許番号
US04525473

関連ノート

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