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 376563노트

반응식

HRID 376563 반응식
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]

참가 물질

6

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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)].

후처리

  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

출처 및 근거

ORD 기록
ord-9281b7a331e94a40b644e5d6a55fc508
출처 데이터셋
uspto-grants-2000_02
특허 번호
US06020329

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