Diethyl Ether → HCID 117892466, compound

HRID 2283386Notes

Reaction equation

HRID 2283386 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5](/[CH:8]=[N:9]/[S@@:10]([C:12]([CH3:15])([CH3:14])[CH3:13])=[O:11])=[C:4]([F:16])[CH:3]=1.[CH2:17]([Mg]Br)[CH3:18].CCOCC.[Cl-].[NH4+]>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([NH:9][S@@:10]([C:12]([CH3:13])([CH3:15])[CH3:14])=[O:11])[CH2:17][CH3:18])=[C:4]([F:16])[CH:3]=1

Participants

7

Reactant 4

HCID 3283Diethyl EtherHCID 25517Ammonium ChlorideHCID 58048503HCID 58048503, compoundHCID 178418443HCID 178418443, compound

Product 1

HCID 117892466HCID 117892466, compoundYield 34%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Step 1 To a solution of (R)-(+)-2-methyl-propane-2-sulfinic acid 1-(4-chloro-2-fluoro-phenyl)-meth-(E)-ylideneamide (50 g, 0.191 mol, 1.0 eq) in THF (1 L) at −75° C. was added 3M ethylmagnesium bromide in Et2O (127.4 ml, 0.382 mol, 2.0 eq) slowly at <−65° C. over 30 min. The reaction was stirred for 2.5 h at <−65° C. before addition of sat. ammonium chloride solution (500 ml). The solution was diluted with water (250 ml) and the organic layer separated. The aqueous layer was extracted with EtOAc (2×500 ml) and the combined organic layers were washed with brine (500 ml), dried over MgSO4, filtered and concentrated in vacuo to afford 59 g of crude material (3:1 mixture of diastereomers by 1H NMR). The crude material was purified by chromatography (silica, 1 Kg) eluting with 20% EtOAc/heptanes up to 30% EtOAc to give (R)-(+)-2-methyl-propane-2-sulfinic acid [(R)-1-(4-chloro-2-fluoro-phenyl)-propyl]-amide (19.9 g, 1H NMR>95%, 0.0682 mol, 34% yield). 1H NMR (270 MHz, CDCl3): 7.27-7.21 (1H, m), 7.13-7.04 (2H, m), 4.43 (1H, q), 3.50 (1H, d), 2.02-1.72 (2H, m), 1.21 (9H, s), 0.89 (3H, t).

Workup

  1. customthe organic layer separated
  2. extractionThe aqueous layer was extracted with EtOAc (2×500 ml)
  3. washthe combined organic layers were washed with brine (500 ml)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customto afford 59 g of crude material (3:1 mixture of diastereomers by 1H NMR)
  8. customThe crude material was purified by chromatography (silica, 1 Kg)
  9. washeluting with 20% EtOAc/heptanes up to 30% EtOAc

Sources & evidence

ORD record
ord-f39125a3cf904dedb7632197cec9123d
Source dataset
uspto-grants-2015_09
Patent number
US09145354B2

Reaction notes

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