Triphenylphosphine → 5-(1-isopropyl-pyrrolidin-3-yloxy)-1H-indole-2-carboxylic acid ethyl ester

HRID 493983Notes

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]C1)([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)=O)=O)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]([CH3:17])[CH3:18])[CH2:21]1)=[CH:10][CH:9]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To a cold (0° C.) mixture of 5-hydroxy-1H-indole-2-carboxylic acid ethyl ester (10 g, 1.0 eq.), 1-isopropyl-piperidin-4-ol (intermediate 1, step 1, 7.32 g, 1.05 eq.) and triphenylphosphine (15.3 g, 1.2 eq.) in tetrahydrofuran (280 ml) was slowly added a solution of diisopropylazodicarboxylate (11.8 g, 1.2 eq.) in tetrahydrofuran (20 mL). The mixture was stirred 30 min at 0° C. and overnight at room temperature, was concentrated in vacuo, dissolved in methyltertiobutylether (310 mL), washed with sodium hydroxide aqueous solution (0.5N), brine, dried over Na2SO4, filtered and evaporated. The residue was purified on silica eluting with dichloromethane/methanol/ammoniac. One fraction was isolated and dried in vacuo, to yield 7.0 g (43%) of the desired product as white solid. MS (m/e): 331.5 (MH+, 100%)

Workup

concentrationwas concentrated in vacuo
dissolutiondissolved in methyltertiobutylether (310 mL)
washwashed with sodium hydroxide aqueous solution (0.5N), brine
dry with materialdried over Na2SO4
filtrationfiltered
customevaporated
customThe residue was purified on silica eluting with dichloromethane/methanol/ammoniac
customOne fraction was isolated
customdried in vacuo

Sources & evidence

ORD record: ord-367be40cf0ed4e758201e7b34c9a7532
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07538101B2

Reaction notes

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