N-Fluorobenzenesulfonimide → tert-butyl 4-chloro-3-fluoro-5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrole-2-carboxylate

HRID 1948378Notes

Reaction equation

Br[C:2]1[C:6]([Cl:7])=[C:5]([CH3:8])[N:4]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:3]=1[C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].[Li]CCCC.C1C=CC(S(N(S(C2C=CC=CC=2)(=O)=O)[F:39])(=O)=O)=CC=1>C1COCC1>[Cl:7][C:6]1[C:2]([F:39])=[C:3]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[N:4]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:5]=1[CH3:8]

Participants

Conditions

Temperature: -78 °C

Procedure

tert-butyl 3-bromo-4-chloro-5-methyl-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrole-2-carboxylate (Intermediate 265, 480 mg, 1.13 mmol) was dissolved in dry THF (8 ml), cooled down to −78° C., n-BuLi (2.5M in Hexane, 3.39 mmol) was added dropwise into the mixture via syringe and the mixture was stirred at −78° C. for 30 min followed by a quick addition of N-Fluorobenzensulfonimide (1.25 g, 3.96 mmol in 5 ml of THF/Toluene 1:1), the resulting mixture was then stirred at −78° C. for 30 min and slowly warmed up to room temperature during a period of 12 hrs. The reaction was quenched at 0° C. with drops of saturated NH4Cl solution and further diluted with EtOAc (50 ml). The organic phase was washed with brine and dried over anhydrous MgSO4, concentrated to an oil and purified by flash column chromatography eluted with 10% EtOAc in Hexanses. The desired product was obtained as an oil (125 mg).

Workup

stirringthe resulting mixture was then stirred at −78° C. for 30 min
temperatureslowly warmed up to room temperature during a period of 12 hrs
customThe reaction was quenched at 0° C. with drops of saturated NH4Cl solution
additionfurther diluted with EtOAc (50 ml)
washThe organic phase was washed with brine
dry with materialdried over anhydrous MgSO4
concentrationconcentrated to an oil
custompurified by flash column chromatography
washeluted with 10% EtOAc in Hexanses

Sources & evidence

ORD record: ord-43b8dc5865594f0ca391ca680599b5a5
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399489B2

Reaction notes

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