Cesium carbonate → Ethyl 3-((1-(2-(tert-butoxy)-2-oxoethyl)-6-chloro-7-fluoro-2-methyl-1H-indol-3-yl) thio)-2-fluorobenzoate

HRID 2171304Notes

Reaction equation

HRID 2171304 reaction equation
[Cl:1][C:2]1[C:10]([F:11])=[C:9]2[C:5]([C:6]([S:13][C:14]3[C:15]([F:25])=[C:16]([CH:22]=[CH:23][CH:24]=3)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:7]([CH3:12])[NH:8]2)=[CH:4][CH:3]=1.Br[CH2:27][C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.[N+](CCCC)(CCCC)(CCCC)CCCC.[Br-].O>[C:31]([O:30][C:28](=[O:29])[CH2:27][N:8]1[C:9]2[C:5](=[CH:4][CH:3]=[C:2]([Cl:1])[C:10]=2[F:11])[C:6]([S:13][C:14]2[C:15]([F:25])=[C:16]([CH:22]=[CH:23][CH:24]=2)[C:17]([O:19][CH2:20][CH3:21])=[O:18])=[C:7]1[CH3:12])([CH3:34])([CH3:33])[CH3:32]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 79177tert-Butyl bromoacetateHCID 667654293-(6-Chloro-7-fluoro-2-methyl-1H-indol-3-ylsulfanyl)-2-fluoro-benzoic acid ethyl ester

Product 1

HCID 117979167Ethyl 3-((1-(2-(tert-butoxy)-2-oxoethyl)-6-chloro-7-fluoro-2-methyl-1H-indol-3-yl) thio)-2-fluorobenzoateYield 112%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of compound 4 (140 mg, 0.36 mmol) in DMF (3 mL) under inert atmosphere were added tert-butyl 2-bromoacetate (0.08 mL, 0.54 mmol), Cs2CO3 (238 mg, 0.73 mmol), Bu4NBr (5.9 mg, 0.018 mmol) at RT and stirred for 1 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with water (20 mL) and extracted with EtOAc (2×20 mL). The combined organic extracts were washed with water (15 mL) dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude compound 5 (200 mg) as a pale green semisolid. 1H NMR (500 MHz, CDCl3): δ 7.61 (t, J=7.0 Hz, 1H), 7.21 (d, J=8.0 Hz, 1H), 7.09 (t, J=8.5 Hz, 1H), 6.90 (t, J=8.5 Hz, 1H), 6.74 (t, J=6.5 Hz, 1H), 4.95 (s, 2H), 4.40 (q, 2H), 2.44 (s, 3H), 1.52 (s, 9H), 1.42 (t, J=7.5 Hz, 3H); LC-MS: 96.7%; 513.6 (M+H2O); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.72 min. 5 mM NH4OAc: ACN; 0.8 mL/min).

Workup

  1. customafter completion of the reaction
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic extracts were washed with water (15 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-fd3a125ec1644a91b120e81a83fa711c
Source dataset
uspto-grants-2015_06
Patent number
US09051320B1

Reaction notes

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