Chloroform → 3-Piperidin-1-yl-1-triisopropylsilanyl-1H-indole

HRID 737013Notes

Reaction equation

[NH:1]1[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[C:18]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[N:20]([Si:27]([CH:34]([CH3:36])[CH3:35])([CH:31]([CH3:33])[CH3:32])[CH:28]([CH3:30])[CH3:29])[CH:19]=1.C(Cl)(Cl)Cl>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[N:1]1([C:18]2[C:26]3[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=3)[N:20]([Si:27]([CH:31]([CH3:33])[CH3:32])([CH:34]([CH3:36])[CH3:35])[CH:28]([CH3:29])[CH3:30])[CH:19]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1

Participants

Conditions

Temperature: 70 °C

Procedure

Dissolve piperidine (1.28 mL, 12.9 mmol) in THF (10 mL) and treat with lithium bis(trimethylsilyl)-amide (1.0M in THF, 11.2 mL, 11.2 mmol). To the above solution add 3-bromo-1-triisopropylsilanyl-1H-indole (TCI-US, 3.04 g, 8.62 mmol), (2′-dicyclohexyl-phosphanyl-biphenyl-2-yl)-dimethyl-amine (88 mg, 0.22 mmol), and Pd2 dba3.CHCl3 (225 mg, 0.22 mmol). Heat the red solution to 70° C. for 4 h then cool to RT and concentrate. Purify the crude material by flash chromatography, using a linear gradient of 100% hexanes to 40% EtOAc/hexanes, to give the title compound (837 mg, 27%). MS (ES+) 357.2 (M+1)+. 1H NMR (400 MHz, CDCl3): δ 7.61 (d, 1H, J=8.4), 7.41 (d, 1H, J=8.4), 7.07 (m, 2H), 6.68 (s, 1H), 3.03 (m, 4H), 1.79 (m, 4H), 1.65 (septet, 3H, J=7.7), 1.58 (m, 2H), 1.12 (d, 18H, J=7.1).

Workup

temperaturethen cool to RT
concentrationconcentrate
customPurify the crude material by flash chromatography

Sources & evidence

ORD record: ord-0ffcde6fa7d543128c2e912720aa5597
Source dataset: uspto-grants-2009_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07595339B2

Reaction notes

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