Methyl trifluoromethyl ketone → 4-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl ester

HRID 639870노트

반응식

HRID 639870 반응식
[Na].[Na].C(N(CC(O)=O)CC(O)=O)CN(CC(O)=O)CC(O)=[O:8].[CH3:23][O:24][C:25]([C:27]1([CH:37]([O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH:38]2[CH2:43][CH2:42][CH2:41][CH2:40][CH2:39]2)[C:31](=[CH2:32])[CH:30]([CH2:33][CH2:34][Cl:35])[C:29](=[O:36])[NH:28]1)=[O:26].FC(F)(F)C(=O)C.C(=O)(O)[O-].[Na+].OOS([O-])=O.[K+]>C(#N)C.O>[CH3:23][O:24][C:25]([C:27]1([CH:37]([O:44][Si:45]([C:48]([CH3:51])([CH3:50])[CH3:49])([CH3:47])[CH3:46])[CH:38]2[CH2:39][CH2:40][CH2:41][CH2:42][CH2:43]2)[NH:28][C:29](=[O:36])[CH:30]([CH2:33][CH2:34][Cl:35])[C:31]21[O:8][CH2:32]2)=[O:26]

참가 물질

8

반응물 5

HCID 9871Methyl trifluoromethyl ketoneHCID 516892Sodium BicarbonateHCID 9949814Ethylenediaminetetraacetic acid disodiumHCID 23707502Potassium hydroxy sulfiteHCID 685773462-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester

생성물 1

HCID 766116584-[(Tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl ester수율 72%

시약·촉매·용매 2

HCID 962Water용매HCID 6342Acetonitrile용매

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온도
0 °C

실험 절차

An aqueous ethylenediaminetetraacetic acid disodium solution (1.04 ml, 4×10−4 M) was added to a stirred solution of 2-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-4-(2-chloro-ethyl)-3-methylene-5-oxo-pyrrolidine-2-carboxylic acid methyl ester (71 mg, 0.16 mmol, 1.0 equiv) in acetonitrile (2.6 ml) and the reaction mixture was cooled to 0° C. Trifluoroacetone (0.6 ml) was added via a precooled syringe. A mixture of sodium bicarbonate (0.313 g, 3.72 mmol, 23.25 equiv) and Oxone (0.738 g, 1.2 mmol, 7.5 equiv) was added. The reaction mixture was stirred for 4 h at 0° C. Water (20 ml) was added and the resultant mixture was extracted with dichloromethane (100 ml). The organic layer was separated, dried over sodium sulfate and the solids were filtered. The filtrate was concentrated. Purification of the residue by flash column chromatography (15% ethyl acetate-hexanes initially, grading to 20% ethyl acetate-hexanes) provided 4-[(tert-butyl-dimethyl-silanyloxy)-cyclohexyl-methyl]-7-(2-chloro-ethyl)-6-oxo-1-oxa-5-aza-spiro[2.4]heptane-4-carboxylic acid methyl ester (53 mg, 72%).

후처리

  1. additionwas added
  2. extractionthe resultant mixture was extracted with dichloromethane (100 ml)
  3. customThe organic layer was separated
  4. dry with materialdried over sodium sulfate
  5. filtrationthe solids were filtered
  6. concentrationThe filtrate was concentrated
  7. customPurification of the residue by flash column chromatography (15% ethyl acetate-hexanes initially

출처 및 근거

ORD 기록
ord-90270c2d430c49c7a55f0f9692434187
출처 데이터셋
uspto-grants-2010_04
특허 번호
US07691896B2

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