Diisobutylaluminum hydride → 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol

HRID 2038128Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([CH3:19])([CH3:18])[CH2:12][C:13](OCC)=[O:14])[NH:8]2)=[CH:4][C:3]=1[N+:20]([O-:22])=[O:21].CC(C[AlH]CC(C)C)C>C(Cl)Cl>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7]([C:11]([CH3:19])([CH3:18])[CH2:12][CH2:13][OH:14])[NH:8]2)=[CH:4][C:3]=1[N+:20]([O-:22])=[O:21]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of ethyl 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutanoate (34 g, 0.11 mol) in dry CH2Cl2 (400 mL) was added drop-wise DIBAL-H (283.4 mL, 0.27 mol) over 2 hours at −78° C. The reaction mixture was stirred for 10 hours at −78° C. and then quenched by adding water (200 mL). The precipitate was filtered off and washed with methanol. The filtrate was extracted with CH2Cl2 (200 mL×3), the combined organic layers were washed with brine, dried over anhydrous Na2SO4 and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:1) to give 3-(6-fluoro-5-nitro-1H-indol-2-yl)-3-methylbutan-1-ol (6.6 g, 22%). 1H NMR (400 MHz, CDCl3) δ 9.35 (brs, 1 H), 8.30 (d, J=7.6 Hz, 1 H), 7.11 (d, J=12.0 Hz, 1 H), 6.35 (d, J=1.2 Hz, 1 H), 3.74 (t, J=6.4 Hz, 2 H), 1.9 (t, J=6.4 Hz, 2 H), 1.4 (s, 6 H).

Workup

customquenched
additionby adding water (200 mL)
filtrationThe precipitate was filtered off
washwashed with methanol
extractionThe filtrate was extracted with CH2Cl2 (200 mL×3)
washthe combined organic layers were washed with brine
dry with materialdried over anhydrous Na2SO4
concentrationconcentrated under reduced pressure
customThe residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 50:1)

Sources & evidence

ORD record: ord-3174623996ab45cd8ebd6c5336be142a
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575209B2

Reaction notes

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