Cesium fluoride → HCID 86700880, compound

HRID 881774Notes

Reaction equation

HRID 881774 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]23[O:14][C:11]([CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])([CH2:12][CH2:13]2)[CH2:10][CH2:9]3)=[CH:4][CH:3]=1.[C:21]([C:25]1[O:29][C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34](B3OC(C)(C)C(C)(C)O3)=[CH:33][CH:32]=2)=[N:27][N:26]=1)([CH3:24])([CH3:23])[CH3:22].[F-].[Cs+].O1CCOCC1>ClCCl.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:21]([C:25]1[O:29][C:28]([NH:30][C:31]2[CH:36]=[CH:35][C:34]([C:2]3[CH:7]=[CH:6][C:5]([C:8]45[O:14][C:11]([CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])([CH2:12][CH2:13]4)[CH2:10][CH2:9]5)=[CH:4][CH:3]=3)=[CH:33][CH:32]=2)=[N:27][N:26]=1)([CH3:24])([CH3:22])[CH3:23]

Participants

8

Reactant 4

HCID 25953Cesium fluorideHCID 312751,4-DioxaneHCID 86700857HCID 86700857, compoundHCID 86700877HCID 86700877, compound

Product 1

HCID 86700880HCID 86700880, compoundYield 74.3%

Reagents, catalysts & solvents 3

HCID 11714597Bis(di-tert-butyl(4-dimethylaminophenyl)phosphine)dichloropalladium(II)CatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
90 °C

Procedure

To a flask charged with methyl 3-(4-(4-bromophenyl)-7-oxabicyclo[2.2.1]heptan-1-yl)propanoate (103 mg, 0.30 mmol), 5-(tert-butyl)-N-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)-1,3,4-oxadiazol-2-amine (109 mg, 0.32 mmol), Pd(amphos)Cl2 (21 mg, 0.030 mmol) and CsF (138 mg, 0.91 mmol) under N2 was added 1,4-dioxane (2.7 mL) and water (0.30 mL). The mixture was sparged with N2 for 10 min and stirred in a 90° C. oil bath for 2 h. The resulting reaction mixture was diluted with dichloromethane and washed with a saturated aqueous NaHCO3 solution. The organic layer was warmed and filtered (no product evident in filtercake). The filtrate was concentrated to afford 200 mg of crude orange solid. The crude material was washed with triturated with acetonitrile and filtered to afford 106 mg of pale orange solid which was used without further purification. 1H NMR (400 MHz, DMSO-d6): δ ppm 1.36 (s, 9H), 1.56-1.83 (m, 6H), 2.04-2.20 (m, 4H), 3.62 (s, 3H), 7.42 (d, J=8.6 Hz, 2H), 7.55-7.69 (m, 6H), 10.51 (s, 1H) (additional 2H signal likely hidden under DMSO solvent peak). ESI-MS m/z: 476.0 [M+H]+, retention time 1.55 min (condition E).

Workup

  1. customThe mixture was sparged with N2 for 10 min
  2. customThe resulting reaction mixture
  3. washwashed with a saturated aqueous NaHCO3 solution
  4. temperatureThe organic layer was warmed
  5. filtrationfiltered (no product evident in filtercake)
  6. concentrationThe filtrate was concentrated
  7. customto afford 200 mg of crude orange solid
  8. washThe crude material was washed
  9. customwith triturated with acetonitrile
  10. filtrationfiltered

Sources & evidence

ORD record
ord-ce554a2f959c462dbb71cc536c18de0b
Source dataset
uspto-grants-2015_03
Patent number
US08993619B2

Reaction notes

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