Diisobutylaluminum hydride → HCID 117833499, compound

Temperature

-78 °C

Intermediate XVI-1: In a dry flask under an inert atmosphere the light yellow solution of (S)-ethyl 3-((S)-1,1-dimethylethylsulfinamido)-4,4-difluoro-3-(2-fluorophenyl)butanoate (XV-2) (2.59 g, 7.09 mmol) in DCM (75 ml) was treated dropwise with DIBAH (1 M in toluene; 10.6 ml, 10.6 mmol) keeping the internal temperature below −72° C. After complete addition the reaction mixture was stirred at −78° C. for 30 min. For the workup, the mixture was quenched with a saturated solution of NH4Cl (10 ml), left to warm to room temperature and stirred for 30 min. The thick suspension was filtered through a layer of Dicalite® which was washed twice with DCM. The filtrate was treated with a half-saturated solution of NH4Cl and extracted three times with DCM. The combined organic layers were dried over MgSO4 and evaporated. The crude product was purified by chromatography on silica gel (eluent: heptane/AcOEt; gradient: 30-50% AcOEt) to yield the (S)—N—((S)-1,1-difluoro-2-(2-fluorophenyl)-4-oxobutan-2-yl)-2-methylpropane-2-sulfinamide (XVI-1) (704 mg, 31% yield) as a light yellow oil and the starting ester XV-2 (1.28 g, 49% yield) as a colorless oil. MS: m/z=322.4 (M+H)+.

1. customthe internal temperature below −72° C
2. additionAfter complete addition the reaction mixture
3. customFor the workup, the mixture was quenched with a saturated solution of NH4Cl (10 ml)
4. waitleft
5. temperatureto warm to room temperature
6. stirringstirred for 30 min
7. filtrationThe thick suspension was filtered through a layer of Dicalite® which
8. washwas washed twice with DCM
9. additionThe filtrate was treated with a half-saturated solution of NH4Cl
10. extractionextracted three times with DCM
11. dry with materialThe combined organic layers were dried over MgSO4
12. customevaporated
13. customThe crude product was purified by chromatography on silica gel (eluent: heptane/AcOEt; gradient: 30-50% AcOEt)

ORD record

ord-6cb3d9841b0341f0abcd9e3b3869c664

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067926B2