tert-butyl 2-[(E)-[(S)-tert-butylsulfinyl]iminomethyl]-1,3-thiazole-5-carboxylate → tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)thiazole-5-carboxylate

HRID 588520Notes

Reaction equation

[C:1]([S@@:5](/[N:7]=[CH:8]/[C:9]1[S:10][C:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:12][N:13]=1)=[O:6])([CH3:4])([CH3:3])[CH3:2].[CH3:21][Mg]Br>C(Cl)Cl>[CH3:2][C:1]([CH3:4])([S@@:5]([NH:7][C@@H:8]([C:9]1[S:10][C:11]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[CH:12][N:13]=1)[CH3:21])=[O:6])[CH3:3]

Participants

Conditions

Temperature: -70 °C

Procedure

To a solution of (S,E)-tert-butyl 2-((tert-butylsulfinylimino)methyl)thiazole-5-carboxylate (15 g, 47 mmol) in DCM (500 mL) at −70° C. was slowly added methylmagnesium bromide (63 mL, 3 M in ether). The mixture was stirred at −70° C. for 3 h then quenched with sat. NH4Cl solution. The solution was then warmed to rt. After separation, the aqueous phase was extracted with DCM (3×200 mL). Combined organic phases were dried (Na2SO4), and concentrated. Flash column chromatography (DCM: MeOH, 100:0 to 100:1) afforded tert-butyl 2-((R)-1-((S)-1,1-dimethylethylsulfinamido)ethyl)thiazole-5-carboxylate (10 g, 64%). 1H NMR (CDCl3, 400 MHz) δ 8.14 (s, 1H), 4.76 (m, 1H), 4.15 (m, 1H), 1.60 (d, J=6.8 Hz, 3H), 1.50 (s, 9H), 1.20 (s, 9H).

Workup

customat −70° C.
customthen quenched with sat. NH4Cl solution
temperatureThe solution was then warmed to rt
customAfter separation
extractionthe aqueous phase was extracted with DCM (3×200 mL)
dry with materialCombined organic phases were dried (Na2SO4)
concentrationconcentrated

Sources & evidence

ORD record: ord-76489e9f8b404515b1a6ccd56e7ceb48
Source dataset: uspto-grants-2016_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09227951B2

Reaction notes

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