1,2-Dichloroethane → Tert-butyl 6,8-dioxo-5-azaspiro[3.5]nonane-5-carboxylate

HRID 1175121노트

반응식

HRID 1175121 반응식
[C:1]([O:5][C:6]([NH:8][C:9]1([CH2:13][C:14]([OH:16])=O)[CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)CCl.[CH3:21][C:22]1(C)OC(=O)CC(=O)[O:23]1.Cl.O>CN(C1C=CN=CC=1)C.C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[C:22](=[O:23])[CH2:21][C:14](=[O:16])[CH2:13][C:9]21[CH2:10][CH2:11][CH2:12]2)=[O:7])([CH3:2])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 111,2-DichloroethaneHCID 162492,2-Dimethyl-1,3-dioxane-4,6-dioneHCID 10751878(1-Aminocyclobut-1-yl)acetic acid, N-BOC protectedHCID 21885828Hydrate;hydrochloride

생성물 1

HCID 59558334Tert-butyl 6,8-dioxo-5-azaspiro[3.5]nonane-5-carboxylate

시약·촉매·용매 2

HCID 142844-(Dimethylamino)pyridine촉매HCID 6344Dichloromethane용매

실험 절차

(1-tert-Butoxycarbonylamino-cyclobutyl)-acetic acid (6 g; 26 mmol) (Eur.J.Med.Chem. 34 (1999) 363), EDC (7.5 g; 39 mmol) DMAP (4.8 g; 39 mmol) and Meldrum's acid (3.77 g; 26 mmol) in CH2Cl2 (120 ml) are stirred at room temperature over night and poured on 2N HCl/water (40 ml/400 ml). The aqueous phase is extracted with CH2Cl2 twice, the organic phases are combined and dried over Na2SO4 and evaporated to dryness. The orange-colored residue is taken up in ethyl acetate (200 ml) and refluxed for 2.5 hours, diluted with hexanes (600 ml) and purified via chromatography (SiO2; Hexanes/acetone 92:8) yielding the title compound as yellowish crystals in a modest purity, which is sufficient to perform the next steps.

후처리

  1. extractionThe aqueous phase is extracted with CH2Cl2 twice
  2. dry with materialdried over Na2SO4
  3. customevaporated to dryness
  4. temperaturerefluxed for 2.5 hours
  5. additiondiluted with hexanes (600 ml)
  6. custompurified via chromatography (SiO2; Hexanes/acetone 92:8)

출처 및 근거

ORD 기록
ord-ccfcf49d365942e0be98591af4459599
출처 데이터셋
uspto-grants-2010_11
특허 번호
US07838674B2

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