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Pyridine → tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate

HRID 376559
ノート
印刷プレビュー

反応式

HRID 376559 の反応式
S(Cl)(C)(=O)=O.Cl.[CH3:7][O:8]/[N:9]=[C:10](/[C:14]1[N:15]=[C:16]([NH:19][C:20]([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:21]2[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=2)[S:17][CH:18]=1)\[C:11](O)=[O:12].C(N(CC)C(C)C)(C)C.[NH2:48][C@@H:49]1[C:68](=[O:69])[N:51]2[C:52]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])=[C:53]([CH:56]3[CH2:60][CH2:59][CH2:58][O:57]3)[CH2:54][S:55][C@H:50]12.N1C=CC=CC=1>CN(C=O)C.C(OCC)(=O)C>[CH3:7][O:8]/[N:9]=[C:10](/[C:14]1[N:15]=[C:16]([NH:19][C:20]([C:21]2[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=2)([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[S:17][CH:18]=1)\[C:11]([NH:48][C@@H:49]1[C:68](=[O:69])[N:51]2[C:52]([C:61]([O:63][C:64]([CH3:65])([CH3:67])[CH3:66])=[O:62])=[C:53]([CH:56]3[CH2:60][CH2:59][CH2:58][O:57]3)[CH2:54][S:55][C@H:50]12)=[O:12]
参加物実験手順後処理出典と根拠反応ノート

参加物

8

反応物 5

HCID 1049PyridineHCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 95660662-(Tritylamino)-alpha-(methoxyimino)-4-thiazoleacetic acid, predominantly syn hydrochlorideHCID 54097811t-Butyl (6R,7R)-7-Amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate

生成物 1

HCID 141582269
tert-butyl (6R,7R)-7-[[(2Z)-2-methoxyimino-2-[2-(tritylamino)-1,3-thiazol-4-yl]acetyl]amino]-8-oxo-3-(oxolan-2-yl)-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylate
収率 84%

試薬・触媒・溶媒 2

HCID 6228Dimethylformamide溶媒2 回HCID 8857Ethyl Acetate溶媒

実験手順

Mesyl chloride (141μl, 1.8mmol) was added to 2-(Z)-methoxyimino-2-(2-tritylaminothiazol-4-yl)acetic acid hydrochloride (0.744g, 1.65mmol) and N,N-diisopropylethylamine (576μl, 3.3mmol) in DMF (5ml) at -40° C. The reaction mixture was stirred 0.5h at -30±10° C. then t-butyl (6R,7R)-7-amino-3-(tetrahydrofuran-2-yl)ceph-3-em-4-carboxylate, more mobile diastereoisomer (0.431g, 1.3mmol) in DMF (5ml) followed by pyridine (1471μl, 1.8mmol) were added. Stirred 1h without further cooling then diluted with ethyl acetate, washed twice with water and with brine, dried, concentrated and flash chromatographed on silica gel eluting with 30,35 and 40% ethyl acetate in hexane to give the title compound as a foam (0.83g, 84%); vmax (CH2Cl2) 3396, 3277, 1782, 1732, 1683, 1526, 1248, 1156 and 1051cm-1 ; δH [(CD3)2SO, 250MHz]1.47 (9H, s), 1.55-1.75 (1H, m), 1.8-2.0 (2H, m), 2.05-2.2 (1H, m), 3.44 and 3.50 (2H, ABq, J18.3Hz), 3.65-3.95 (2H, m), 3.81 (3H, s), 4.6-4.7 (1H, m), 5.14 (1H, d, J4.8Hz), 5.66 (1H, dd, J4.8, 7.9Hz), 6.70 (1H, s), 7.2-7.4 (15H, m), 8.88 (1H, s) and 9.54 (1H, d, J7.9Hz). [Mass spectrum: +ve ion (3-nitrobenzyl alcohol, sodium acetate) MNa+ (774)].

後処理

  1. additionwere added
  2. temperaturewithout further cooling
  3. washwashed twice with water and with brine
  4. customdried
  5. concentrationconcentrated
  6. customflash chromatographed on silica gel eluting with 30,35 and 40% ethyl acetate in hexane

出典と根拠

ORDレコード
ord-aa3496bd25d646e2b394919c7c0d6492
出典データセット
uspto-grants-2000_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06020329

反応ノート

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