Triethylamine → benzhydryl (6R,7R)-3-(bromomethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-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 2164437ノート

反応式

HRID 2164437 の反応式
[C:1]([O:5][C:6]([CH2:8][O:9]/[N:10]=[C:11](/[C:15]1[N:16]=[C:17]([NH:20][C:21]([C:34]2[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=2)([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[S:18][CH:19]=1)\[C:12](O)=[O:13])=[O:7])([CH3:4])([CH3:3])[CH3:2].P(Cl)(Cl)(Cl)(Cl)Cl.C(N(CC)CC)C.Cl.[NH2:54][C@@H:55]1[C:80](=[O:81])[N:57]2[C:58]([C:64]([O:66][CH:67]([C:74]3[CH:79]=[CH:78][CH:77]=[CH:76][CH:75]=3)[C:68]3[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=3)=[O:65])=[C:59]([CH2:62][Br:63])[CH2:60][S:61][C@H:56]12>ClCCl.O>[Br:63][CH2:62][C:59]1[CH2:60][S:61][C@@H:56]2[C@H:55]([NH:54][C:12](=[O:13])/[C:11](=[N:10]\[O:9][CH2:8][C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])/[C:15]3[N:16]=[C:17]([NH:20][C:21]([C:28]4[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=4)([C:34]4[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=4)[C:22]4[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=4)[S:18][CH:19]=3)[C:80](=[O:81])[N:57]2[C:58]=1[C:64]([O:66][CH:67]([C:68]1[CH:73]=[CH:72][CH:71]=[CH:70][CH:69]=1)[C:74]1[CH:75]=[CH:76][CH:77]=[CH:78][CH:79]=1)=[O:65]

参加物

7

反応物 4

HCID 8471Triethylamine2 回HCID 24819Phosphorus pentachloride2 回HCID 13078701(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetic acidHCID 131714150diphenylmethyl (6R,7R)-7-amino-3-bromomethyl-ceph-3-em-4-carboxylate hydrochloride

生成物 1

HCID 172953016benzhydryl (6R,7R)-3-(bromomethyl)-7-[[(2Z)-2-[2-[(2-methylpropan-2-yl)oxy]-2-oxoethoxy]imino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate収率 85.6%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 6344Dichloromethane溶媒3 回

実験手順

(Z)-2-(t-Butoxycarbonylmethoxyimino)-2-(2-tritylaminothiazol-4-yl)acetic acid (1.1 g) (described in Example 3 of South African Specification No. 78/1630) was added to a stirred solution of phosphorus pentachloride (0.46 g) in dichloromethane (20 ml) at -20°. The solution was kept at -15°±5° for 40 35 minutes. More phosphorus pentachloride (0.05 g) was added after 30 minutes. The solution was cooled to -20° and triethylamine (0.6 ml) was added. The solution was stirred at -20° for 5 minutes and then added to a stirred solution of diphenylmethyl (6R,7R)-7-amino-3-bromomethylceph-3-em-4-carboxylate, hydrochloride salt (1 g) in dichloromethane (20 ml) containing triethylamine (0.3 ml) at -20°. The temperature did not exceed -20° during the addition. The mixture was stirred at -20° for 10 minutes and then warmed to 22° over 45 minutes. The mixture was diluted with water (25 ml) and dichloromethane (20 ml) and shaken. The organic phase was separated and the aqueous layer was backwashed once with dichloromethane. The organic phase was washed with dilute sodium bicarbonate solution and the aqueous phase was backwashed. The combined organic solutions were washed with dilute brine, dried over sodium sulphate, and evaporated to a foam. This was triturated with diisopropyl ether, filtered, and dried in vacuo at 60° for 2 hours followed by room temperature overnight to give the title compound, (1.7 g), [α]D21 -28° (c 1.0 CHCl3); λinf. (ethanol) 239 nm, E1 cm1% 252; 260 nm, E1 cm1% 196; 265.5 nm, E1cm1% 193; 273 nm, E1 cm1% 181.

後処理

  1. customwas kept at -15°±5° for 40 35 minutes
  2. temperatureThe solution was cooled to -20°
  3. additionThe temperature did not exceed -20° during the addition
  4. stirringThe mixture was stirred at -20° for 10 minutes
  5. temperaturewarmed to 22° over 45 minutes
  6. stirringshaken
  7. customThe organic phase was separated
  8. washThe organic phase was washed with dilute sodium bicarbonate solution
  9. washThe combined organic solutions were washed with dilute brine
  10. dry with materialdried over sodium sulphate
  11. customevaporated to a foam
  12. customThis was triturated with diisopropyl ether
  13. filtrationfiltered
  14. customdried in vacuo at 60° for 2 hours
  15. waitfollowed by room temperature overnight

出典と根拠

ORDレコード
ord-c3d0195b0708452abf53825879b414dd
出典データセット
uspto-grants-1985_03
特許番号
US04504477

反応ノート

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