Ethyl Acetate → HCID 86608823, compound

HRID 2055588Notes

Reaction equation

HRID 2055588 reaction equation
[F:1][C:2]1[CH:7]=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:5]=[CH:4][C:3]=1[C@H:17]([NH:19][C:20]([C:22]1([NH:25][C:26](=[O:31])[C:27]([F:30])([F:29])[F:28])[CH2:24][CH2:23]1)=[O:21])[CH3:18].Br[C:33]1[CH:34]=[CH:35][CH:36]=[C:37]2[C:42]=1[N:41]=[CH:40][CH:39]=[CH:38]2.C(=O)([O-])[O-].[Cs+].[Cs+].CCOC(C)=O>O1CCOCC1.[Pd].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>[F:1][C:2]1[CH:7]=[C:6]([C:33]2[CH:34]=[CH:35][CH:36]=[C:37]3[C:42]=2[N:41]=[CH:40][CH:39]=[CH:38]3)[CH:5]=[CH:4][C:3]=1[C@H:17]([NH:19][C:20]([C:22]1([NH:25][C:26](=[O:31])[C:27]([F:29])([F:30])[F:28])[CH2:23][CH2:24]1)=[O:21])[CH3:18]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 1401098-BromoquinolineHCID 86608822HCID 86608822, compound

Product 1

HCID 86608823HCID 86608823, compound

Reagents, catalysts & solvents 2

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 312751,4-DioxaneSolvent

Procedure

N-{(1R)-1-[2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide (250 mg, 0.563 mmol), 8-bromoquinoline (117 mg, 0.563 mmol), cesium carbonate (367 mg, 1.13 mmol), and bis(tri-t-butylphosphine) palladium(0) (10 mg, 0.03 mmol) were stirred in 1 mL of anhydrous dioxane overnight at 90° C. in a sealed tube. The reaction mixture was cooled to room temperature and diluted w/EtOAc. The organic layer was separated, washed with water and brine, dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude material was purified by silica gel chromatography eluting with 10% to 95% EtOAc/hexanes to provide (N-[(1R)-1-(2-fluoro-4-quinolin-8-ylphenyl)ethyl]-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide. ES MS, M+H+ found: 475. Proton NMR (400 MHz, CDCl3) δ 1.2 (m, J=2.4 Hz, 2H), 1.58 (d, J=6.8 Hz, 3H), 1.7 (m, J=2.9 Hz, 2H), 3.86 (s, 3H), 5.33 (q, J=7.2 Hz, 1H), 6.64 (d, J=8.8 Hz, 1H), 6.84 (s, 1H), 7.08 to 7.19 (m, 3H), 7.34 (m, 3H), 7.47 (m, J=4.5 Hz, 1H), 7.81 (m, J=5 Hz, 1H), 7.9 (d, J=9 Hz, 1H).

Workup

  1. customThe organic layer was separated
  2. washwashed with water and brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe crude material was purified by silica gel chromatography
  7. washeluting with 10% to 95% EtOAc/hexanes

Sources & evidence

ORD record
ord-88083181dc024667bb48132727ce824f
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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