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Triphenylphosphine → 5-(1-Isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 19840
Notes
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Reaction equation

HRID 19840 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([OH:15])=[CH:10][CH:9]=2)=[O:5])[CH3:2].[CH:16]([N:19]1[CH2:24][CH2:23][CH:22](O)[CH2:21][CH2:20]1)([CH3:18])[CH3:17].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)(C)C)=O)=O)(C)C>O1CCCC1>[CH2:1]([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[CH:12][C:11]([O:15][CH:22]1[CH2:23][CH2:24][N:19]([CH:16]([CH3:18])[CH3:17])[CH2:20][CH2:21]1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]
ParticipantsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 796811-Isopropylpiperidin-4-ol2×HCID 90677Ethyl 5-hydroxy-1H-indole-2-carboxylateHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylate

Product 1

HCID 441852465-(1-Isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl esterYield 66.9%

Reagents, catalysts & solvents

1
HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (0° C.) solution of 5-hydroxyindole-2-carboxylic acid ethyl ester (purchased at Biosynth, ref H-6350, 20 g, 1.0 eq.), 1-isopropylpiperidin-4-ol (intermediate 1, step 1, 16.75 g, 1.2 eq.) and triphenylphosphine (30.68 g, 1.2 eq.) in tetrahydrofuran (500 mL) was slowly added a solution of di-tert-butylazodicarboxylate (26.93 g, 1.2 eq.) in tetrahydrofuran (100 mL). The reaction mixture was stirred at room temperature for 48 h then evaporated to dryness in vacuo and purified on silica, eluting with a gradient of solvent from dichloromethane/ethyl acetate 19:1 to dichloromethane/methanol/ammonium hydroxide 95:5:0.25. One fraction was isolated and dried in vacuo, to yield 21.53 g (66%) of the desired product as white solid. MS (m/e): 331.1 (MH+, 100%).

Workup

  1. customthen evaporated to dryness in vacuo
  2. custompurified on silica
  3. washeluting with a gradient of solvent from dichloromethane/ethyl acetate 19:1 to dichloromethane/methanol/ammonium hydroxide 95:5:0.25
  4. customOne fraction was isolated
  5. customdried in vacuo

Sources & evidence

ORD record
ord-75b64925e93947979722ad6a0bb1f118
Source dataset
uspto-grants-2010_06
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07745479B2

Reaction notes

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On this pageParticipantsProcedureWorkupSources & evidenceReaction notes