Triethyl phosphonoacetate → HCID 131735598, compound
Reaction equation
[Li+].[Cl-].C(OP([CH2:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])(OCC)=O)C.C(N(CC)C(C)C)(C)C.[CH3:26][C:27]([S@:30]([NH:32][C@:33]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[F:48])([C:37]([F:41])([F:40])[CH:38]=O)[CH:34]([F:36])[F:35])=[O:31])([CH3:29])[CH3:28]>C(#N)C>[C:27]([S@:30]([NH:32][C@@:33]([C:42]1[CH:47]=[CH:46][CH:45]=[CH:44][C:43]=1[F:48])([CH:34]([F:35])[F:36])[C:37]([F:40])([F:41])[CH:38]=[CH:11][C:12]([O:14][CH2:15][CH3:16])=[O:13])=[O:31])([CH3:26])([CH3:28])[CH3:29]Participants
Conditions
- Temperature
- 25 °C
Procedure
To a stirred suspension of LiCl (405 mg, 9.56 mmol) in acetonitrile (30 mL) under N2 were added ethyl 2-diethoxyphosphorylacetate (2.14 g, 9.56 mmol) and DIPEA (N,N-diisopropylethylamine) (2.06 g, 15.94 mmol) at 0° C. After 20 min, (R)-2-methyl-N—((S)-1,1,3,3-tetrafluoro-2-(2-fluorophenyl)-4-oxo-butan-2-yl)propane-2-sulfinamide (2.85 g, 7.97 mmol) in acetonitrile (10 mL) was added dropwise to the mixture at 0° C. and the mixture was stirred at 25° C. for 17.5 hours. The reaction mixture was concentrated to remove acetonitrile, water (50 ml) was added and extracted with ethyl acetate (200 ml). The organic layer was dried and evaporated. The crude product was purified by column chromatography (petrolium ether: ethyl acetate=5:1 to 4:1) to afford ethyl (S)-5-(((R)-tert-butylsulfinyl)amino)-4,4,6,6-tetrafluoro-5-(2-fluorophenyl)hex-2-enoate (1.77 g, 46.8% yield).
Workup
- concentrationThe reaction mixture was concentrated
- customto remove acetonitrile, water (50 ml)
- additionwas added
- extractionextracted with ethyl acetate (200 ml)
- customThe organic layer was dried
- customevaporated
- customThe crude product was purified by column chromatography (petrolium ether: ethyl acetate=5:1 to 4:1)
Sources & evidence
- ORD record
- ord-301a93c1a50c4c7699849a0ab53301a7
- Source dataset
- uspto-grants-2016_05
- Patent number
- US09346797B1
Reaction notes
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