Cesium carbonate → HCID 86760612, compound

HRID 2055583Notes

Reaction equation

HRID 2055583 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[C:42]2[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=2)[CH:36]=[CH:35][C:34]=1[O:43][CH3:44].C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.CCOC(C)=O.[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[C:42]3[C:37](=[CH:38][CH:39]=[CH:40][CH:41]=3)[CH:36]=[CH:35][C:34]=2[O:43][CH3:44])[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:28])[F:29])[CH2:23][CH2:24]1)=[O:21])[CH3:18]

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 728601-Bromo-2-methoxynaphthaleneHCID 86608822HCID 86608822, compound

Product 1

HCID 86760612HCID 86760612, compound

Reagents, catalysts & solvents 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 8857Ethyl AcetateSolventHCID 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, (1 g, 2.25 mmol), 1-bromo-2-methoxynaphthalene (534 mg (2.25 mmol), cesium carbonate (1.47 g 4.5 mmol), and bis(tri-t-butylphosphine) palladium (0) (6 mg 0.1 mmol) were stirred in anhydrous dioxane (4 mL) at 90 C overnight in a sealed tube. The reaction was cooled to room temperature and diluted with EtOAc, washed once each with water and brine. The organic layers were dried over sodium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by silica gel chromatography eluting with 0% to 50% EtOAc/hex. To afford N-{(1R)-1-[2-fluoro-4-(2-methoxy-1-naphthyl)phenyl]ethyl}-1-[(trifluoroacetyl)amino]cyclopropanecarboxamide LC/MS (ES MS, M+H+ found: 475) and 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. washwashed once each with water and brine
  2. dry with materialThe organic layers were dried over sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel chromatography
  6. washeluting with 0% to 50% EtOAc/hex

Sources & evidence

ORD record
ord-214961e00e474a14a87e46c21c325c78
Source dataset
uspto-grants-2008_02
Patent number
US07332499B2

Reaction notes

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