Triphenylphosphine → 6-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 1786473Notes

Reaction equation

HRID 1786473 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])=[C:10]([Cl:16])[CH:9]=2)=[O:5])[CH3:2].[CH:17]([N:20]1[CH2:25][CH2:24][CH:23](O)[CH2:22][CH2:21]1)([CH3:19])[CH3:18].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:23]1[CH2:24][CH2:25][N:20]([CH:17]([CH3:19])[CH3:18])[CH2:21][CH2:22]1)=[C:10]([Cl:16])[CH:9]=2)=[O:5])[CH3:2]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 796811-Isopropylpiperidin-4-olHCID 6034084Di-tert-butyl diazene-1,2-dicarboxylateHCID 670179146-Chloro-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester

Product 1

HCID 670179266-Chloro-5-(1-isopropyl-piperidin-4-yloxy)-1H-indole-2-carboxylic acid ethyl esterYield 67%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cold (0° C.) mixture of 6-chloro-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester (625 mg, 1.0 eq.), 1-Isopropyl-piperidin-4-ol (448 mg, 1.2 eq.) and triphenylphosphine (846 mg, 1.2 eq.) in tetrahydrofuran (8 mL) was added dropwise a solution of di-tert-butylazodicarboxylate (725 mg, 1.2 eq.) in tetrahydrofuran (7 mL). The reaction mixture was stirred for 20 h at room temperature. The volatile components were evaporated under reduced pressure and the residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol/ammonia from 98:2:0 to 90:9:1 as eluant to afford 635 mg (67%) of the tide compound as a light-yellow foam.

Workup

  1. customThe volatile components were evaporated under reduced pressure
  2. customthe residue was purified by flash chromatography on silica gel with a gradient of dichloromethane/methanol/ammonia from 98:2:0 to 90:9:1 as eluant

Sources & evidence

ORD record
ord-3bc6f73e9bb3468996e0477624b39e75
Source dataset
uspto-grants-2009_03
Patent number
US07507736B2

Reaction notes

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