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

HRID 493992Notes

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]([Br: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].C(P(CCCC)CCCC)CCC.N(C(OC(C)(C)C)=O)=NC(OC(C)(C)C)=O>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]([Br:16])[CH:9]=2)=[O:5])[CH3:2]

Participants

Conditions

Temperature: 0 °C

Procedure

To the suspension of 0.25 g (0.88 mmol) 6-bromo-5-hydroxy-1H-indole-2-carboxylic acid ethyl ester in 5 mL tetrahydrofuran, 0.15 g (1.05 mmol) 1-isopropyl-piperidin-4-ol (commercially available) and 0.28 g (1.07 mmol) tributylphosphine were added. The suspension was cooled to 0° C., 0.244 g (1.06 mmol) di-tert-butyl azodicarboxylate was added and the reaction was allowed to reach room temperature. After 48 hours the suspension was filtered and the filtrate was evaporated. The residue was flash-chromatographed on silica gel with a gradient of dichloromethane:methanol (100:0 to 60:40 v/v) to give 0.20 g (55%) of the product as a light yellow foam. MS (m/e): 409.0 (M−H+, 100%).

Workup

additionwere added
customto reach room temperature
filtrationAfter 48 hours the suspension was filtered
customthe filtrate was evaporated
customThe residue was flash-chromatographed on silica gel with a gradient of dichloromethane:methanol (100:0 to 60:40 v/v)

Sources & evidence

ORD record: ord-49eda51a63cd441ebe5c32d9829cbf8d
Source dataset: uspto-grants-2009_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07538101B2

Reaction notes

Loading…