Cesium fluoride → HCID 86700875, compound

HRID 881768Notes

Reaction equation

HRID 881768 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]23[O:14][C:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])([CH2:12][CH2:13]2)[CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[C:20]([C:24]1[O:28][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33](B3OC(C)(C)C(C)(C)O3)=[CH:32][CH:31]=2)=[N:26][N:25]=1)([CH3:23])([CH3:22])[CH3:21].[F-].[Cs+].O1CCOCC1>CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.CC(P(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)C.Cl[Pd]Cl.O>[C:20]([C:24]1[O:28][C:27]([NH:29][C:30]2[CH:35]=[CH:34][C:33]([C:2]3[CH:7]=[CH:6][C:5]([C:8]45[O:14][C:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])([CH2:12][CH2:13]4)[CH2:10][CH2:9]5)=[CH:4][CH:3]=3)=[CH:32][CH:31]=2)=[N:26][N:25]=1)([CH3:23])([CH3:21])[CH3:22]

Participants

7

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 86700857HCID 86700857, compoundHCID 86700872HCID 86700872, compound

Product 1

HCID 86700875HCID 86700875, compoundYield 74.2%

Reagents, catalysts & solvents 2

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

To a flask charged with methyl 2-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)acetate (106 mg, 0.33 mmol), 5-(tert-butyl)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,4-oxadiazol-2-amine (117 mg, 0.34 mmol), Pd(amphos)Cl2 (23 mg, 0.033 mmol) and CsF (150 mg, 0.98 mmol) under N2 was added 1,4-dioxane (2.9 mL) and water (0.33 mL). The mixture was sparged with N2 for 10 min and set to stir in a 90° C. oil bath for 2 hr. The reaction mixture was diluted with ethyl acetate, washed with a saturated aqueous NaHCO3 solution, then water, followed by a saturated aqueous NaCl solution. The organic phase was dried over MgSO4, filtered and concentrated by rotary evaporation in vacuo to afford 210 mg crude orange solid. The crude material was triturated with warm acetonitrile to afford 113 mg of the title compound as a white solid which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.36 (s, 9H), 1.66-1.83 (m, 4H), 1.88-2.00 (m, 2H), 2.10-2.21 (m, 2H), 2.94 (s, 2H), 3.64 (s, 3H), 7.42 (d, J=8.6 Hz, 2H), 7.55-7.71 (m, 6H), 10.52 (s, 1H). ESI-MS m/z: 462.1 [M+H]+, retention time 1.51 min (condition E).

Workup

  1. customThe mixture was sparged with N2 for 10 min
  2. additionThe reaction mixture was diluted with ethyl acetate
  3. washwashed with a saturated aqueous NaHCO3 solution
  4. dry with materialThe organic phase was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated by rotary evaporation in vacuo
  7. customto afford 210 mg crude orange solid
  8. customThe crude material was triturated with warm acetonitrile

Sources & evidence

ORD record
ord-100a5ac6a5a94e51b745c38913fc908c
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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