Sodium Carbonate → HCID 67816096, compound

HRID 2401433Notes

Reaction equation

HRID 2401433 reaction equation
Cl[C:2]1[C:3]2[CH:18]=[C:17]([Cl:19])[CH:16]=[CH:15][C:4]=2[C:5]2[C:9]([CH3:10])=[N:8][O:7][C:6]=2[C:11]2([N:14]=1)[CH2:13][CH2:12]2.[F:20][C:21]1[CH:26]=[CH:25][C:24](B(O)O)=[CH:23][CH:22]=1.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:19][C:17]1[CH:16]=[CH:15][C:4]2[C:5]3[C:9]([CH3:10])=[N:8][O:7][C:6]=3[C:11]3([CH2:13][CH2:12]3)[N:14]=[C:2]([C:24]3[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=3)[C:3]=2[CH:18]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 67818192HCID 67818192, compound

Product 1

HCID 67816096HCID 67816096, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Conditions

Temperature
82 °C

Procedure

To a solution of 6,8-dichloro-1-methylspiro[benzo[e]isoxazolo[5,4-c]azepine-4,1′-cyclopropane] (61.9 mg, 0.211 mmol) in toluene (22 mL) was added 4-fluorophenylboronic acid (37 mg, 0.264 mmol) and Pd(Ph3P)4 (11.22 mg, 9.71 μmol). The reaction was evacuated and purged with N2 (g) (3×), followed by addition of aqueous Na2CO3 (211 μl, 0.422 mmol, 2 M). The reaction was heated to 82° C. for 15 min at which time LC-MS analysis indicated complete conversion to desired product. The reaction mixture was cooled to room temperature and diluted with water. The aqueous layer was extracted with EtOAc (3×) and the combined organic extracts were dried over Na2SO4, and concentrated in vacuo. The crude product was purified on Biotage system (5% EtOAc:95% Hexanes to 10% EtOAc:90% Hexanes). The product 8-chloro-6-(4-fluorophenyl)-1-methylspiro[benzo[e]isoxazolo[5,4-c]azepine-4,1′-cyclopropane] (62 mg, 0.176 mmol, 83% yield) was obtained as a white crystals. LC/MS m/z 353 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 7.81-7.77 (m, 1H), 7.75-7.71 (m, 1H), 7.45-7.38 (m, 2H), 7.19-7.26 (m, 3H), 2.52 (s, 3H), 1.29 (s, 4H).

Workup

  1. customThe reaction was evacuated
  2. custompurged with N2 (g) (3×)

Sources & evidence

ORD record
ord-125b908292524b848b610b23e12034a2
Source dataset
uspto-grants-2014_08
Patent number
US08796261B2

Reaction notes

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