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

HRID 2279313Notes

Reaction equation

HRID 2279313 reaction equation
[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]

Participants

6

Reactant 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

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

[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).

Workup

  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)

Sources & evidence

ORD record
ord-41663b17c9f54224bcc9ffa87a01e266
Source dataset
uspto-grants-2015_09
Patent number
US09133219B2

Reaction notes

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