HCID 86721094, compound → HCID 86721093, compound

HRID 516205Notes

Reaction equation

HRID 516205 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@@H:8]([NH:12][S@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH2:9][CH:10]=[CH2:11])[C:3]=1[F:19].ClC1C=CN=C(/C=N/[S@](C(C)(C)C)=O)C=1F.C([Mg]Br)C=C>C1COCC1.C(O)(C)C.CCCCCCC>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C@H:8]([NH:12][S@:13]([C:15]([CH3:18])([CH3:17])[CH3:16])=[O:14])[CH2:9][CH:10]=[CH2:11])[C:3]=1[F:19]

Participants

7

Reactant 3

HCID 86721094HCID 86721094, compound2×HCID 90199529HCID 90199529, compoundHCID 178455850HCID 178455850, compound

Product 1

HCID 86721093HCID 86721093, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolventHCID 8900HeptaneSolvent

Conditions

Temperature
-78 °C

Procedure

(S)-N-((S)-1-(4-Chloro-3-fluoropyridin-2-yl)but-3-en-1-yl)-2-methylpropane-2-sulfinamide: To a solution of (S,E)-N-((4-chloro-3-fluoropyridin-2-yl)methylene)-2-methylpropane-2-sulfinamide (1.03 g, 3.92 mmol) in THF (100 mL) was added allyl magnesium bromide (1 M in ether) (4.70 mL, 4.70 mmol) dropwise and the resulting solution was stirred for 1 h at −78° C. The reaction mixture was then warmed to rt and then quenched with saturated NH4Cl solution. The reaction mixture was extracted with EtOAc (3×). The combined organic layers were concentrated in vacuo, and the residue was then subjected to silica gel purification to provide a mixture of the S and R isomers. MS (ESI) m/z: 305.1 (M+H)+. Chiral separation: AD column eluting with 30% isopropanol in heptane provided peak 1 as the desired (S)-N-((S)-1-(4-Chloro-3-fluoropyridin-2-yl)but-3-en-1-yl)-2-methylpropane-2-sulfinamide (0.710 g, 59%) and peak2 as (S)-N-((R)-1-(4-chloro-3-fluoropyridin-2-yl)but-3-en-1-yl)-2-methylpropane-2-sulfinamide (0.081 g, 7% yield).

Workup

  1. temperatureThe reaction mixture was then warmed to rt
  2. customquenched with saturated NH4Cl solution
  3. extractionThe reaction mixture was extracted with EtOAc (3×)
  4. concentrationThe combined organic layers were concentrated in vacuo
  5. customthe residue was then subjected to silica gel purification
  6. customto provide
  7. additiona mixture of the S and R isomers
  8. customChiral separation

Sources & evidence

ORD record
ord-0e15de13e4414ec38e3a8563083160ff
Source dataset
uspto-grants-2015_08
Patent number
US09108981B2

Reaction notes

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