Ammonium Chloride → [2-(3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-4-(2-methoxy-ethoxymethoxy)-phenyl]-carbamic Acid Tert-Butyl Ester

HRID 29012

반응식

HRID 29012 반응식
[C:1]([CH:3]1[CH2:5][CH2:4]1)#[CH:2].C([Li])CCC.[C:11]([O:15][C:16](=[O:37])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:20][C:19]=1[C:31](=[O:36])[C:32]([F:35])([F:34])[F:33])([CH3:14])([CH3:13])[CH3:12].[Cl-].[NH4+]>ClCCl.C(O)(C)C.C1COCC1>[C:11]([O:15][C:16](=[O:37])[NH:17][C:18]1[CH:23]=[CH:22][C:21]([O:24][CH2:25][O:26][CH2:27][CH2:28][O:29][CH3:30])=[CH:20][C:19]=1[C:31]([OH:36])([C:32]([F:35])([F:34])[F:33])[C:2]#[C:1][CH:3]1[CH2:5][CH2:4]1)([CH3:14])([CH3:12])[CH3:13]

참가 물질

8

반응물 4

HCID 25517Ammonium ChlorideHCID 138823CyclopropylacetyleneHCID 68801075[4-(2-methoxy-ethoxymethoxy)-2-(2,2,2-trifluoro-acetyl)-phenyl]-carbamic Acid Tert-Butyl EsterHCID 178418339Butyllithium

생성물 1

HCID 68800268[2-(3-cyclopropyl-1-hydroxy-1-trifluoromethyl-prop-2-ynyl)-4-(2-methoxy-ethoxymethoxy)-phenyl]-carbamic Acid Tert-Butyl Ester수율 61%

시약·촉매·용매 3

HCID 3776Isopropanol용매HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

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온도
-40 °C

실험 절차

A solution of 200 μL (2.3 mmol) of ethynyl-cyclopropane in 2 mL of freshly distilled THF was cooled to −40° C. and 1 mL (2.5 mmol) of n-butyl lithium (2.5M in hexane) was added under argon atmosphere. The reaction mixture was allowed to stir at −40° C. for 10 minutes. To the reaction mixture a solution of 400 mg (1.0 mmol) of 6 in 4 mL of freshly distilled THF was added, and the reaction was allowed to stir at −40° C. for 15 minutes. To the reaction mixture 2 mL of isopropanol were added followed by 20 mL of saturated ammonium chloride solution at −40° C. The reaction mixture was warmed up to room temperature, and 30 mL of dichloromethane was added. The organic layer was separated, and the aqueous layer was extracted with 3×30 mL of dichloromethane. The organic layers were combined, dried (anhydrous Na2SO4), and concentrated under reduced pressure. The residue was purified by silica gel flash column chromatography using 20% ethyl acetate in hexane to give 280 mg (0.61 mmol, 60%) of 7 [LC-MS; M+Na 482.2].

후처리

  1. stirringto stir at −40° C. for 15 minutes
  2. temperatureThe reaction mixture was warmed up to room temperature
  3. customThe organic layer was separated
  4. extractionthe aqueous layer was extracted with 3×30 mL of dichloromethane
  5. dry with materialdried (anhydrous Na2SO4)
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel flash column chromatography

출처 및 근거

ORD 기록
ord-7190fe031c90434b9b9c213db980248f
출처 데이터셋
uspto-grants-2008_09
특허 번호
US07420043B2

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