Cesium carbonate → 3-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-(6-fluoro-quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

HRID 1948891Notes

Reaction equation

HRID 1948891 reaction equation
[CH2:1]([O:3][C:4](=[O:32])[C:5]([CH3:31])([CH3:30])[CH2:6][C:7]1[N:8]([CH2:22][C:23]2[CH:28]=[CH:27][C:26]([Br:29])=[CH:25][CH:24]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([OH:21])=[CH:11][CH:10]=2)[CH3:2].Br[CH2:34][C:35]1[CH:44]=[CH:43][C:42]2[C:37](=[CH:38][CH:39]=[C:40]([F:45])[CH:41]=2)[N:36]=1.C([O-])([O-])=O.[Cs+].[Cs+]>CC#N>[CH2:1]([O:3][C:4](=[O:32])[C:5]([CH3:31])([CH3:30])[CH2:6][C:7]1[N:8]([CH2:22][C:23]2[CH:24]=[CH:25][C:26]([Br:29])=[CH:27][CH:28]=2)[C:9]2[C:14]([C:15]=1[S:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[CH:13][C:12]([O:21][CH2:34][C:35]1[CH:44]=[CH:43][C:42]3[C:37](=[CH:38][CH:39]=[C:40]([F:45])[CH:41]=3)[N:36]=1)=[CH:11][CH:10]=2)[CH3:2]

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 216180422-(Bromomethyl)-6-fluoroquinolineHCID 444742653-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester

Product 1

HCID 568495523-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-(6-fluoro-quinolin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl esterYield 71.9%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To 3-[1-(4-Bromo-benzyl)-3-tert-butylsulfanyl-5-hydroxy-1H-indol-2-yl]-2,2-dimethyl-propionic acid ethyl ester (C-3; 2.0 g, 3.9 mmol) in MeCN (25 mL) was added 2-bromomethyl-6-fluoro-quinoline (1.0 g, 4.2 mmol), and Cs2CO3 (2.5 g, 7.7 mmol). The reaction was stirred at room temperature overnight, after which LCMS showed the reaction was complete. The reaction mixture was partitioned between EtOAc and water, the aqueous layer was extracted with EtOAc, and the combined organic layers were dried over MgSO4, filtered, and concentrated. The residue was recrystallized in EtOAc:hexane to give the desired product (F-1, 1.9 g). The filtrate was concentrated and purified on silica gel (0 to 15% EtOAc in hexanes) to give an additional 1 g of F-1.

Workup

  1. customThe reaction mixture was partitioned between EtOAc and water
  2. extractionthe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was recrystallized in EtOAc

Sources & evidence

ORD record
ord-6d3eeced76fd4753a7f0856e5a1651e3
Source dataset
uspto-grants-2013_03
Patent number
US08399666B2

Reaction notes

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