Methanesulfonyl chloride → N-methanesulfonyl-6-nitroindole

HRID 889436Notes

Reaction equation

[N+:1]([C:4]1[CH:12]=[C:11]2[C:7]([CH:8]=[CH:9][NH:10]2)=[CH:6][CH:5]=1)([O-:3])=[O:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[CH3:23][S:24](Cl)(=[O:26])=[O:25]>C1COCC1>[CH3:23][S:24]([N:10]1[C:11]2[C:7](=[CH:6][CH:5]=[C:4]([N+:1]([O-:3])=[O:2])[CH:12]=2)[CH:8]=[CH:9]1)(=[O:26])=[O:25]

Participants

Conditions

Temperature: -78 °C

Procedure

To a solution of 6-nitro-1H-indole (0.250 g, 1.54 mmol) in dry THF (15.4 mL) at −78° C. under nitrogen was added sodium bis(trimethylsilyl)amide (1.850 mL, 1.850 mmol) dropwise via syringe. The resulting solution was stirred for 20 minutes at −78° C., followed by addition of methanesulfonyl chloride (0.14 mL, 1.85 mmol) dropwise via syringe. Following the addition, the cooling bath was removed, and the mixture was allowed to warm to room temperature. After 1 hour, the suspension was filtered, and the resulting solid was taken up in 10 mL of aqueous MeOH and heated to reflux. The hot mixture was filtered to afford a light yellow solid which was dried in vacuo, furnishing Intermediate 64A (0.208 g, 56% yield) as a light yellow solid. HPLC: Rt=3.160 min. (YMC S5 ODS 4.6×50 mm, 10-90% aqueous methanol containing 0.2% H3PO4, 4 min. gradient, monitored at 220 nm). MS (ES): m/z=241.0 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 8.70 (1H, d, J=2.01 Hz), 8.18 (1H, dd, J=8.81, 2.01 Hz), 7.98 (1H, d, J=3.78 Hz), 7.92 (1H, d, J=8.81 Hz), 7.05 (1H, d, J=3.78 Hz), 3.55-3.66 (3H, m).

Workup

additionthe addition
customthe cooling bath was removed
temperatureto warm to room temperature
waitAfter 1 hour
filtrationthe suspension was filtered
temperatureheated to reflux
filtrationThe hot mixture was filtered
customto afford a light yellow solid which
customwas dried in vacuo

Sources & evidence

ORD record: ord-20a01b4893f343ddb1ab3c855637c513
Source dataset: uspto-grants-2012_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08252795B2

Reaction notes

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