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 1036839Notes

Reaction equation

HRID 1036839 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-9f616b9a259d4589898524f732b059a3
Source dataset
uspto-grants-2013_10
Patent number
US08546431B2

Reaction notes

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