tert-Butylsulfinamide, (R)-(+)- → HCID 90373422, compound

HRID 930431Notes

Reaction equation

[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1[C:9](=O)[CH3:10].[CH3:12][C:13]([S@:16]([NH2:18])=[O:17])([CH3:15])[CH3:14]>O1CCCC1.[Cl-].[Na+].O.CCOC(C)=O.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][C:3]=1/[C:9](=[N:18]\[S@@:16]([C:13]([CH3:15])([CH3:14])[CH3:12])=[O:17])/[CH3:10]

Participants

Conditions

Temperature: 65 °C

Procedure

To a solution of 1-(2-chloro-3-fluorophenyl)ethanone (31.21 g, 181 mmol) in tetrahydrofuran (500 mL) was added (R)-2-methylpropane-2-sulfinamide (32.9 g, 271 mmol) and titanium(IV) isopropoxide (111 mL, 371 mmol). The mixture was heated to 65° C. overnight. LCMS showed 25% starting material remaining. Additional 16 g sulfinamide and 30 mL Ti(OPr)4 was added and the reaction was continued at 70° C. overnight. The mixture was diluted with brine (600 mL), and EtOAc. The solid was filtered through a pad of celite and washed with EtOAc. The organic layer was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. The crude material was purified by silica gel chromatography (330 g, 0-60% EtOAc-hexane in 20 min) to give (R,Z)-N-(1-(2-chloro-3-fluorophenyl)ethylidene)-2-methylpropane-2-sulfinamide (40.8 g, 82% yield) as yellow oil. MS m/z=276 [M+H]+. Calculated for C12H15ClFOS: 275.8.

Workup

filtrationThe solid was filtered through a pad of celite
washwashed with EtOAc
washThe organic layer was washed with brine
dry with materialdried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customThe crude material was purified by silica gel chromatography (330 g, 0-60% EtOAc-hexane in 20 min)

Sources & evidence

ORD record: ord-8d3fa49f0dc34e46987988f044b87fe2
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296734B2

Reaction notes

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