Pyridine → methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(R)-fluoropropionate

HRID 1008285ノート

反応式

HRID 1008285 の反応式
[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@H:6](O)[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4].N1C=CC=CC=1.S(OS(C(F)(F)F)(=O)=O)(C(F)(F)[F:36])(=O)=O>C(Cl)Cl>[CH2:1]([C@@H:5]([C:12]([N:14]1[CH2:18][CH2:17][CH2:16][C@H:15]1[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[O:13])[C@@H:6]([F:36])[C:7]([O:9][CH3:10])=[O:8])[CH2:2][CH2:3][CH3:4]

参加物

5

反応物 3

HCID 1049PyridineHCID 67749Trifluoromethanesulfonic anhydrideHCID 59908531methyl 3-(R)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-yl-carbonyl)-2-(S)-hydroxypropionate

生成物 1

HCID 59908476methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(R)-fluoropropionate収率 45%

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

反応条件

温度
-20 °C

実験手順

To methyl 3-(R)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-ylcarbonyl)-2-(S)-hydroxypropionate G-3 (5 mmol) in DCM (5 mL) was added pyridine (15 mmol), the reaction was cooled to −20° C., then triflic anhydride was added (7.5 mmol). The solution was stirred for 1 hour, then washed with aqueous citric acid, sodium bicarbonate and brine, then dried (Na2SO4) and concentrated. The intermediate triflate was then resuspended in DCM and cooled to −50° C. Tris(dimethylamino)sulfur (trimethylsilyl)difluoride (TAS-F) was added (5 mmol) and the solution allowed to warm to rt. The reaction mixture was washed with aqueous sodium bicarbonate and brine, dried (Na2SO4) and concentrated then purified on silica gel (ethylacetate/hexanes) to afford 2.3 mmol (45%) of methyl 3-(S)-n-butyl-3-[2-(S)-tert-butoxycarbonylpyrrolidin-1-yl-carbonyl)-2-(R)-fluoropropionate G-4.

後処理

  1. washwashed with aqueous citric acid, sodium bicarbonate and brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. temperaturecooled to −50° C
  5. additionTris(dimethylamino)sulfur (trimethylsilyl)difluoride (TAS-F) was added (5 mmol)
  6. temperatureto warm to rt
  7. washThe reaction mixture was washed with aqueous sodium bicarbonate and brine
  8. dry with materialdried (Na2SO4)
  9. concentrationconcentrated
  10. customthen purified on silica gel (ethylacetate/hexanes)

出典と根拠

ORDレコード
ord-84fb141af9a14f8ab8616a1ed0fc70ff
出典データセット
uspto-grants-2004_09
特許番号
US06797820B2

反応ノート

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