Trifluoroacetic acid → (1S,2S)-ethyl 2-(4-((1R)-7-fluoro-4-(3-methoxypyridin-2-yl)-2,3-dihydro-1H-inden-1-yloxy)phenyl)cyclopropanecarboxylate

HRID 471457Notes

Reaction equation

HRID 471457 reaction equation
[CH2:1]([O:3][C:4]([C@H:6]1[CH2:8][C@@H:7]1[C:9]1[CH:14]=[CH:13][C:12]([O:15][C@H:16]2[C:24]3[C:19](=[C:20](B4OC(C)(C)C(C)(C)O4)[CH:21]=[CH:22][C:23]=3[F:25])[CH2:18][CH2:17]2)=[CH:11][CH:10]=1)=[O:5])[CH3:2].Br[C:36]1[C:41]([O:42][CH3:43])=[CH:40][CH:39]=[CH:38][N:37]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C(O)(C(F)(F)F)=O>[Pd](Cl)Cl.C(P(C(C)(C)C)[C-]1C=CC=C1)(C)(C)C.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2].CN(C)C=O>[F:25][C:23]1[CH:22]=[CH:21][C:20]([C:36]2[C:41]([O:42][CH3:43])=[CH:40][CH:39]=[CH:38][N:37]=2)=[C:19]2[C:24]=1[C@H:16]([O:15][C:12]1[CH:11]=[CH:10][C:9]([C@H:7]3[CH2:8][C@@H:6]3[C:4]([O:3][CH2:1][CH3:2])=[O:5])=[CH:14][CH:13]=1)[CH2:17][CH2:18]2

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 10796Cesium carbonateHCID 903642-Bromo-3-methoxypyridineHCID 86703891(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester2×

Product 1

HCID 86703890(1S,2S)-ethyl 2-(4-((1R)-7-fluoro-4-(3-methoxypyridin-2-yl)-2,3-dihydro-1H-inden-1-yloxy)phenyl)cyclopropanecarboxylateYield 26.8%

Reagents, catalysts & solvents 2

HCID 178454861HCID 178454861, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

(1S,2S)-2-{4-[(R)-7-Fluoro-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-indan-1-yloxy]-phenyl}-cyclopropanecarboxylic acid ethyl ester (Intermediate 24, 46.6 mg) and 2-bromo-3-methoxypyridine (28.2 mg) are dissolved N,N-dimethylformamide (1 mL) and degassed with a flow of argon. Aqueous 2M cesium carbonate solution (0.1 mL), 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (6.5 mg, 0.1 equiv.) are added and the mixture is heated at 80° C. for 2.5 hours under argon. The reaction mixture is acidified with 50% aq. TFA, filtered over basic aluminium oxide and the filter material is washed with N,N-dimethylformamide. The crude product is purified by reversed phase chromatography to give the title compound (Yield 12.0 mg).

Workup

  1. customdegassed with a flow of argon
  2. filtrationfiltered over basic aluminium oxide
  3. washthe filter material is washed with N,N-dimethylformamide
  4. customThe crude product is purified by reversed phase chromatography

Sources & evidence

ORD record
ord-02501b03d8304f9aa7f802c275ee4a07
Source dataset
uspto-grants-2014_01
Patent number
US08633182B2

Reaction notes

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