Dimethyl Sulfoxide → 2-Methyltetrahydrofuran

HRID 1908225Notes

Reaction equation

F[C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-:10])=[O:9])=[C:4]([C:11]([F:14])([F:13])[F:12])[CH:3]=1.[C:15](=[O:18])([O-])[O-].[Na+].[Na+].CS(C)=O.Cl.[CH:26]12[NH:32][CH:29]([CH2:30][CH2:31]1)[CH2:28][CH2:27]2>CC1CCCO1>[N+:8]([C:5]1[CH:6]=[CH:7][C:2]([N:32]2[CH:26]3[CH2:31][CH2:30][CH:29]2[CH2:28][CH2:27]3)=[CH:3][C:4]=1[C:11]([F:14])([F:13])[F:12])([O-:10])=[O:9].[CH3:7][CH:2]1[CH2:3][CH2:4][CH2:15][O:18]1

Participants

Conditions

Temperature: 55 °C

Procedure

4-fluoro-1-nitro-2-(trifluoromethyl)benzene (18) (901 g) was added into a 30 L jacketed vessel. Sodium carbonate (959.1 g) and 5 L dimethylsulfoxide (DMSO) was added and the mixture was stirred under a nitrogen atmosphere. 7-azabicyclo[2.2.1]heptane hydrochloride (7a) (633.4 g) was added to the vessel in portions. The temperature of the mixture was gradually raised to 55° C., and the reaction was monitored by HPLC. When the substrate was less than 1% AUC, the reaction was considered complete. The mixture was then diluted with 10 vol. 2-methyltetrahydrofuran and washed with 5.5 vol. water three times until no DMSO remained in the aqueous layer as determined by HPLC, to give 7-[4-nitro-3-(trifluoromethyl) phenyl]-7-azabicyclo[2.2.1]heptane (19) in 2-methyltetrahydrofuran (approximately 95% yield).

Workup

washwashed with 5.5 vol. water three times until no DMSO

Sources & evidence

ORD record: ord-db3e5e5d6a8c4e48a742f4edc626a208
Source dataset: uspto-grants-2013_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08598205B2

Reaction notes

Loading…