Methanol → Methyl (δS)-δ-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-3,5-difluoro-α,α-dimethylbenzenepentanoate

HRID 1367130ノート

反応式

HRID 1367130 の反応式
[F:1][C:2]1[CH:3]=[C:4]([C:9](=O)[CH2:10][CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])[CH:5]=[C:6]([F:8])[CH:7]=1.[CH3:20][C:21]([S@@:24]([NH2:26])=[O:25])([CH3:23])[CH3:22].[BH4-].[Na+].CO>C1COCC1.[Cl-].[Na+].O.[O-]CC.[O-]CC.[O-]CC.[O-]CC.[Ti+4]>[C:21]([S@@:24]([NH:26][C@H:9]([C:4]1[CH:3]=[C:2]([F:1])[CH:7]=[C:6]([F:8])[CH:5]=1)[CH2:10][CH2:11][C:12]([CH3:18])([CH3:17])[C:13]([O:15][CH3:16])=[O:14])=[O:25])([CH3:23])([CH3:22])[CH3:20]

参加物

8

反応物 4

HCID 887MethanolHCID 4311764Sodium borohydrideHCID 11355477tert-Butylsulfinamide, (S)-(-)-HCID 57974028Methyl 3,5-difluoro-α,α-dimethyl-δ-oxobenzenepentanoate

生成物 1

HCID 66864959Methyl (δS)-δ-[[(S)-(1,1-dimethylethyl)sulfinyl]amino]-3,5-difluoro-α,α-dimethylbenzenepentanoate

試薬・触媒・溶媒 3

HCID 76524Titanium tetraethoxide触媒HCID 8028Tetrahydrofuran溶媒HCID 57417360Sodium chloride; water溶媒

実験手順

To a solution of methyl 5-(3,5-difluorophenyl)-2,2-dimethyl-5-oxopentanoate from Step D (500. mg, 1.85 mmol) and (S)-2-methylpropane-2-sulfinamide (336 mg, 2.78 mmol) in THF (6.5 mL), was added titanium tetraethoxide (616 mg, 2.52 mmol). The reaction vessel was quickly sealed and placed into a 60° C. bath for 3 hours. After cooling to ambient temperature a septum and nitrogen inlet were attached prior to cooling to 0° C. Sodium borohydride (191 mg, 5.05 mmol) was then added, and a complete reaction was observed after 15 minutes. Methyl alcohol was then slowly added until gas evolution had stopped. The reaction mixture was then diluted with saturated brine (6.5 mL) while experiencing rapid stirring. The resultant slurry was filtered through celite, washing with EtOAc as needed. The combined organics were then washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to give an oil. This oil was purified by silica gel chromatography, eluting with a gradient of EtOAc:Hexanes—10:90 to 70:30, to give the title compound containing about 12% of the corresponding ethyl ester. MS: m/z=376 (M+1).

後処理

  1. customThe reaction vessel was quickly sealed
  2. customplaced into a 60° C.
  3. customfor 3 hours
  4. temperatureto cooling to 0° C
  5. customa complete reaction
  6. filtrationThe resultant slurry was filtered through celite
  7. washwashing with EtOAc
  8. washThe combined organics were then washed with brine
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo
  12. customto give an oil
  13. customThis oil was purified by silica gel chromatography
  14. washeluting with a gradient of EtOAc

出典と根拠

ORDレコード
ord-a64fe89c93b940e483dccae663d9676c
出典データセット
uspto-grants-2011_02
特許番号
US07893079B2

反応ノート

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