2,6-Lutidine → t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

HRID 376563ノート

反応式

HRID 376563 の反応式
O[CH:2]([N:10]1[C@H:13]([S:14][CH2:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[O:17])[C@H:12]([NH:24][C:25](=[O:33])[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:11]1=[O:34])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4].N1C(C)=CC=CC=1C.S(Cl)([Cl:45])=O.C(OCC)(=O)C>C1COCC1>[Cl:45][CH:2]([N:10]1[C@H:13]([S:14][CH2:15][C:16]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][O:19]2)=[O:17])[C@H:12]([NH:24][C:25](=[O:33])[CH2:26][C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[C:11]1=[O:34])[C:3]([O:5][C:6]([CH3:9])([CH3:8])[CH3:7])=[O:4]

参加物

6

反応物 4

HCID 79372,6-LutidineHCID 8857Ethyl AcetateHCID 24386Thionyl ChlorideHCID 18397160t-Butyl 2-hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

生成物 1

HCID 54090620t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

実験手順

t-Butyl 2-hydroxy-2-[(3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate (1.9g) in dry THF (10ml) was treated with 2,6-lutidine (0.62g, 0.67ml) followed by thionyl chloride (0.69g, 0.42ml) in THF (5ml) dropwise at <-20° C. under argon. The reaction mixture was allowed to warm slowly to ca 0° C. at which point no starting material was observed by t.l.c. (ethyl acetate). The reaction mixture was filtered and solvent removed in vacuo, the residue dissolved in toluene and evaporated to afford crude t-butyl (RS)-2-chloro-2-((3R,4R)-3-phenylacetamido-4-[(RS)-tetrahydropyran-2-ylcarbonylmethylthio]azetidin-2-on-1-yl]acetate as a brown gum. This was dissolved in dry dioxan (10ml) and treated with tri-n-butylphosphine (1.79g, 2.2ml). The reaction mixture was stirred until loss of starting material was observed by t.l.c. (ethyl acetate) ca 0.5h. After removal of solvent in vacuo the title compound was obtained by flash chromatography (eluting with 50,60,80% ethyl acetate in hexane, ethyl acetate) as a pale brown foam (1.95g, 75%); vmax (CH2Cl2) 3417(w), 1762, 1681, 1625cm-1. [Mass spectrum +ve ion (thioglycerol) MH+ (677)].

後処理

  1. temperatureto warm slowly to ca 0° C. at which point no starting material
  2. filtrationThe reaction mixture was filtered
  3. customsolvent removed in vacuo
  4. dissolutionthe residue dissolved in toluene
  5. customevaporated

出典と根拠

ORDレコード
ord-9281b7a331e94a40b644e5d6a55fc508
出典データセット
uspto-grants-2000_02
特許番号
US06020329

反応ノート

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