Dichloromethane → 2-({6-(3-Pentanoyl-1-benzofuran-2-yl)-1-[4-(trifluoromethyl)phenyl]-2-naphthyl}oxy)acetonitrile

HRID 1359219Notes

Reaction equation

Br[C:2]1[C:11]2[C:6](=[CH:7][C:8]([C:12]3[O:13][C:14]4[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=4[C:16]=3[C:17](=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21])=[CH:9][CH:10]=2)[CH:5]=[CH:4][C:3]=1[O:27][CH2:28][C:29]#[N:30].[F:31][C:32]([F:43])([F:42])[C:33]1[CH:38]=[CH:37][C:36](B(O)O)=[CH:35][CH:34]=1.ClCCl.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[C:17]([C:16]1[C:15]2[CH:23]=[CH:24][CH:25]=[CH:26][C:14]=2[O:13][C:12]=1[C:8]1[CH:9]=[C:10]2[C:5](=[CH:6][CH:7]=1)[C:4]([C:36]1[CH:37]=[CH:38][C:33]([C:32]([F:43])([F:42])[F:31])=[CH:34][CH:35]=1)=[C:3]([O:27][CH2:28][C:29]#[N:30])[CH:2]=[CH:11]2)(=[O:22])[CH2:18][CH2:19][CH2:20][CH3:21]

Participants

Conditions

Temperature: 77 °C

Procedure

Following the procedure described in Step 1 of Example 1, 2-{[1-bromo-6-(3-pentanoyl-1-benzofuran-2-yl)-2-naphthyl]oxy}acetonitrile (0.476 g, 1.03 mmol) was coupled to 4-trifluoromethylphenylboronic acid (0.785 g, 4.13 mmol), using [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium (II) complex with dichloromethane (1:1) (0.088 g, 0.108 mmol) and potassium carbonate (0.301 g, 2.18 mmol) in dioxane (10 mL) and water (1 mL). The reaction mixture was heated at 77° C. for 16 hours. Purification by flash chromatography (Biotage apparatus) using 2-10% ethyl acetate in hexane as an eluant yielded 2-({6-(3-pentanoyl-1-benzofuran-2-yl)-1-[4-(trifluoromethyl)phenyl]-2-naphthyl}oxy)acetonitrile as a yellow wax (0.364 g); 1HNMR (300 MHz, DMSO-d6): δ8.55 (s, 1H), 8.35 (d, 1H, J=8.5 Hz), 8.05 (d, 1H, J=7.7 Hz), 7.95 (d, 2H, J=7.7 Hz), 7.75-7.85 (m, 2H), 7.75 (d, 1H, J=7.7 Hz), 7.35-7.5 (m, 3H), 5.3 (s, 2H), 2.75 (t, 2H, J=7.7 Hz), 1.5-1.6 (m, 2H), 1.1-1.25 (m, 2H), and 0.7 (t, 3H, J=7.7 Hz).

Workup

customPurification by flash chromatography (Biotage apparatus)

Sources & evidence

ORD record: ord-d75468a37cc040b9981d98b0b286f461
Source dataset: uspto-grants-2003_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06599925B2

Reaction notes

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