Cesium fluoride → 3-Phenyl-3-{5-[2-(5,6,7,8-tetrahydro-[1,8]naphthyridin-2-yl)-ethoxy]-indol-1-yl}-propionic acid

HRID 1295140Notes

Reaction equation

[F-].[Cs+].C(OC([N:10]1[C:19]2[C:14](=[CH:15][CH:16]=[C:17]([CH2:20][CH2:21][O:22][C:23]3[CH:24]=[C:25]4[C:29](=[CH:30][CH:31]=3)[NH:28][CH:27]=[CH:26]4)[N:18]=2)[CH2:13][CH2:12][CH2:11]1)=O)(C)(C)C.[C:32]1([C:38]#[C:39][C:40]([O:42]CC)=[O:41])[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C=O)C.O.C(OCC)(=O)C>[C:32]1([CH:38]([N:28]2[C:29]3[C:25](=[CH:24][C:23]([O:22][CH2:21][CH2:20][C:17]4[CH:16]=[CH:15][C:14]5[CH2:13][CH2:12][CH2:11][NH:10][C:19]=5[N:18]=4)=[CH:31][CH:30]=3)[CH:26]=[CH:27]2)[CH2:39][C:40]([OH:42])=[O:41])[CH:33]=[CH:34][CH:35]=[CH:36][CH:37]=1

Participants

Conditions

Temperature: 60 °C

Procedure

CsF (15.2 g, 100 mmol) was added to a solution of 7-[2-(1H-indol-5-yloxy)-ethyl]-3,4-dihydro-2H-[1,8]naphthyridine-1-carboxylic acid tert-butyl ester (20.0 g, 50.8 mmol) in anhydrous DMF (50 mL). Ethyl phenylpropiolate (16.5 mL, 100 mmol) was added to the mixture at room temperature and the solution was allowed to stir under a nitrogen atmosphere at 60° C. for 4 h. The mixture was diluted with water (1 L), the crude mixture was dissolved in ethyl acetate (500 mL), washed with water, then brine, dried and concentrated under vacuum to give a yellow gum as crude product. Purification of the crude mixture on silica gel (1:1 pet-ether/ether) gave the title compound as a bright yellow solid (25.5 g, 88% yield), a mixture of E/Z isomers.

Workup

washwashed with water
dry with materialbrine, dried
concentrationconcentrated under vacuum
customto give a yellow gum as crude product
customPurification of the crude mixture on silica gel (1:1 pet-ether/ether)

Sources & evidence

ORD record: ord-b89384cacd6041c49ed5441cfd4774b4
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07241789B2

Reaction notes

Loading…