Potassium Carbonate → 6-fluoro-5-[4-(3-hydroxyoxetan-3-yl)-3-methoxyphenyl]-1H-indole-3-carbaldehyde

HRID 338289Notes

Reaction equation

CC1(C)COB([C:8]2[CH:13]=[CH:12][C:11]([C:14]3([OH:18])[CH2:17][O:16][CH2:15]3)=[C:10]([O:19][CH3:20])[CH:9]=2)OC1.Br[C:23]1[CH:24]=[C:25]2[C:29](=[CH:30][C:31]=1[F:32])[NH:28][CH:27]=[C:26]2[CH:33]=[O:34].C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.C(O)C.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]>[F:32][C:31]1[CH:30]=[C:29]2[C:25]([C:26]([CH:33]=[O:34])=[CH:27][NH:28]2)=[CH:24][C:23]=1[C:8]1[CH:13]=[CH:12][C:11]([C:14]2([OH:18])[CH2:15][O:16][CH2:17]2)=[C:10]([O:19][CH3:20])[CH:9]=1

Participants

Conditions

Temperature: 110 °C

Procedure

To a solution of 3-[4-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)-2-methoxyphenyl]oxetan-3-ol (101 mg, 0.348 mmol) and 5-bromo-6-fluoro-1H-indole-3-carbaldehyde (88.5 mg, 0.365 mmol) in toluene/ethanol (8 mL, 3:1) was added 2N potassium carbonate (145 mg, 1.051 mmol) and Pd(dppf)Cl2 (30 mg, 0.041 mol). The reaction was degassed with N2 for 2 minutes. The reaction was heated to 110° C. for 3 hours. The reaction mixture was concentrated to give a crude residue, which was purified by column chromatography on a silica gel to afford the title compound (86 mg, 73%) as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 8.80 (br. s, 1H), 8.32 (d, 1H), 7.79 (d, 1H), 7.32 (d, 1H), 7.15 (m, 2H), 7.07 (s, 1H), 3.88 (s, 3H), 3.62 (s, 1H), 2.50 (m, 2H), 2.34 (m, 2H), 1.98 (m, 1H), 1.64 (m, 1H)

Workup

customThe reaction was degassed with N2 for 2 minutes
concentrationThe reaction mixture was concentrated
customto give a crude residue, which
customwas purified by column chromatography on a silica gel

Sources & evidence

ORD record: ord-17a439a8307241998e4e77baea4bdbd9
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889730B2

Reaction notes

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