Carbon Dioxide → 6-fluoro-1-(triisopropylsilyl)-1H-indole-5-carboxylic acid

HRID 634297Notes

Reaction equation

[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])=[CH:4][CH:3]=1.C([Li])(CC)C.C1CCCCC1.[C:32](=[O:34])=[O:33]>CCOCC.O.C1COCC1>[F:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][N:8]2[Si:11]([CH:15]([CH3:17])[CH3:16])([CH:18]([CH3:20])[CH3:19])[CH:12]([CH3:13])[CH3:14])=[CH:4][C:3]=1[C:32]([OH:34])=[O:33]

Participants

Conditions

Temperature: -75 °C

Procedure

In a 250 mL round bottomed flask, 6-fluoro-1-(triisopropylsilyl)-1H-indole (5.12 g, 17.57 mmol) was treated with THF (35 mL), cooled to −75° C. and treated with sec-butyllithium, 1.4 M in cyclohexane (12.55 mL, 17.57 mmol) and stirred at −75° C. for 2 h. The reaction mixture was treated with crushed dry ice and was warmed to RT over 30 min. The reaction mixture was treated with 10 mL water and the organic layer was washed with 1 M citric acid (2×20 mL) in an extraction funnel. The organic layer was then concentrated under reduced pressure (rotary evaporator) and recrystallized from a 9:1 mixture of hexanes:Et2O (100 mL) overnight in the freezer affording 6-fluoro-1-(triisopropylsilyl)-1H-indole-5-carboxylic acid (4.36 g, 13.00 mmol, 74.0% yield) as a white crystalline solid. MS (ESI, pos. ion) m/z: 336.0 (M+H)+. 1H NMR (400 MHz, CDCl3) δ ppm 8.25 (1H, d, J=7.4 Hz), 7.26 (1H, d, J=3.1 Hz), 7.20 (1H, d, J=12.9 Hz), 6.65 (1H, d, J=2.9 Hz), 1.68 (3H, quin, J=7.5 Hz), 1.14 (18H, d, J=7.6 Hz).

Workup

temperaturewas warmed to RT over 30 min
washthe organic layer was washed with 1 M citric acid (2×20 mL) in an extraction funnel
concentrationThe organic layer was then concentrated under reduced pressure (rotary evaporator)
customrecrystallized from a 9:1 mixture of hexanes

Sources & evidence

ORD record: ord-ef65d84dab7c435d99fdf86cf7f2f27b
Source dataset: uspto-grants-2016_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09321756B2

Reaction notes

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