Triphenylphosphine → {1-[2-(6-Methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester

HRID 1422714노트

반응식

HRID 1422714 반응식
[C:1]([O:5][C:6](=[O:17])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:14][CH2:15][OH:16])[CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:18][O:19][C:20]1[N:21]=[C:22]2[C:27](=[CH:28][CH:29]=1)[N:26]=[CH:25][C:24](O)=[CH:23]2.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>O1CCCC1>[C:1]([O:5][C:6](=[O:17])[NH:7][CH:8]1[CH2:9][CH2:10][N:11]([CH2:14][CH2:15][O:16][C:24]2[CH:25]=[N:26][C:27]3[C:22]([CH:23]=2)=[N:21][C:20]([O:19][CH3:18])=[CH:29][CH:28]=3)[CH2:12][CH2:13]1)([CH3:4])([CH3:2])[CH3:3]

참가 물질

6

반응물 4

HCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 45076484[1-(2-Hydroxy-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl esterHCID 1363794146-Methoxy-[1,5]naphthyridin-3-ol

생성물 1

HCID 66747260{1-[2-(6-Methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester수율 45.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

실험 절차

[1-(2-hydroxy-ethyl)-piperidin-4-yl]-carbamic acid tert-butyl ester (50 mg, 0.19 mmol, 1.0 eq) is added at room temperature to a stirred solution of 6-methoxy-[1,5]naphthyridin-3-ol (37 mg, 0.19 mmol, 1.0 eq) in tetrahydrofuran (5 mL), followed by triphenylphosphine polymer-bound (3 mmol/g, 193 mg, 0.58 mmol, 3.0 eq) and diisopropyl azodicarboxylate (115 μL, 0.58 mmol, 3.0 eq). After 3 hours stirring at room temperature, the polymer-bound is filtered off and washed successively with tetrahydrofuran (5 mL), dichloromethane (5 mL) and methanol (5 mL). The resulting solution is concentrated and the residue is extracted with ethyl acetate (3×10 mL) and water (10 mL). The combined organic layers are dried over sodium sulfate, filtered and concentrated to give a crude that is purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 4:1:0 to 0:9:1, v/v/v) to afford {1-[2-(6-methoxy-[1,5]naphthyridin-3-yloxy)-ethyl]-piperidin-4-yl}-carbamic acid tert-butyl ester as an orange solid (35 mg, 33% yield).

후처리

  1. filtrationthe polymer-bound is filtered off
  2. washwashed successively with tetrahydrofuran (5 mL), dichloromethane (5 mL) and methanol (5 mL)
  3. concentrationThe resulting solution is concentrated
  4. extractionthe residue is extracted with ethyl acetate (3×10 mL) and water (10 mL)
  5. dry with materialThe combined organic layers are dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give a crude that
  9. customis purified by column chromatography (silica gel, eluent: cyclohexane:ethyl acetate:methanol, 4:1:0 to 0:9:1, v/v/v)

출처 및 근거

ORD 기록
ord-f3d9d40f79ba49128fc427378739b5a0
출처 데이터셋
uspto-grants-2015_01
특허 번호
US08927542B2

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