Hexamethylphosphoramide → Benzhydryl 7-(2-thienylacetamido)-3-(4-hydroxybutanoyloxymethyl)-2-cephem-4-carboxylate

HRID 259396

反応式

HRID 259396 の反応式
[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:35](=[O:36])[N:12]2[C:13]([C:19]([O:21][CH:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])=[C:14]([CH2:17]Br)[CH2:15][S:16][C@H:11]12)=[O:8].CN(C)P(N(C)C)(N(C)C)=O.[OH:48][CH2:49][CH2:50][CH2:51][C:52]([O-:54])=[O:53].[Na+]>C(OCC)(=O)C>[S:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][C:7]([NH:9][CH:10]1[C:35](=[O:36])[N:12]2[CH:13]([C:19]([O:21][CH:22]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)[C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)=[O:20])[C:14]([CH2:17][O:54][C:52](=[O:53])[CH2:51][CH2:50][CH2:49][OH:48])=[CH:15][S:16][C@H:11]12)=[O:8]

参加物

5

反応物 3

HCID 12679Hexamethylphosphoramide2 回HCID 23663870Sodium OxybateHCID 70634766Benzhydryl 7-(2-thienylacetamido)-3-bromomethyl-3-cephem-4-carboxylate

生成物 1

HCID 131710853Benzhydryl 7-(2-thienylacetamido)-3-(4-hydroxybutanoyloxymethyl)-2-cephem-4-carboxylate

試薬・触媒・溶媒 1

HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of 2.24 g. (3.8 mmol) of benzhydryl 7-(2-thienylacetamido)-3-bromomethyl-3-cephem-4-carboxylate in 20 ml. of hexamethylphosphoramide (HMPA) at 0° C. under nitrogen was added a suspension of 0.530 g. (4.2 mmol) of sodium 4-hydroxybutanoate in 25 ml. of HMPA. After stirring 1.5 hours, ethyl acetate was added, and the resulting solution was washed with water (5X) and brine and dried over anhydrous MgSO4. Evaporation in vacuo to dryness provided 2.12 g. of product which was combined with that of an identical reaction ran on a 1 mmol scale. The combined products were chromatographed on a silica gel column using a cyclohexane:ethyl acetate (1:2) eluant to provide 293 mg. of a mixture of the title product and the corresponding 3-cephem compound. For the title product: nmr (CDCl3) δ1.7-2.6 ##STR26## 3.55 (m, 2, CH2OH), 3.83 (s, 2, side chain CH2), 4.63 (bs, 1, --CH2OH), 5.0 (s, 1, C4 --H), 5.23 (d, 1, J = 4 Hz, C6 --H), 5.58 (dd, 1, J = 4 and 8 Hz, C7 --H), 6.42 (bs, 1, C2 --H), 6.95 (s, 1, ester CH), and 7.36 (m, 13, thienyl + ArH).

後処理

  1. additiona suspension of 0.530 g
  2. washthe resulting solution was washed with water (5X) and brine
  3. dry with materialdried over anhydrous MgSO4
  4. customEvaporation in vacuo to dryness
  5. customprovided 2.12 g
  6. customof an identical reaction
  7. customThe combined products were chromatographed on a silica gel column
  8. customto provide 293 mg

出典と根拠

ORDレコード
ord-eaf780383c304188828ec1b9c6543e33
出典データセット
uspto-grants-1977_07
特許番号
US04038275

関連ノート

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