Water → 2-Tert-butoxycarbonylamino-3-difluoromethoxy-butyric acid methyl ester

HRID 1751355

反応式

HRID 1751355 の反応式
[CH3:1][O:2][C:3](=[O:16])[CH:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:5]([OH:7])[CH3:6].FS([C:21]([F:26])([F:25])C(O)=O)(=O)=O.O>C(#N)C.C(OCC)(=O)C.[Cu]I>[CH3:1][O:2][C:3](=[O:16])[CH:4]([NH:8][C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[CH:5]([O:7][CH:21]([F:26])[F:25])[CH3:6]

参加物

7

反応物 3

HCID 962WaterHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acid2 回HCID 4351132Methyl 2-{[(tert-butoxy)carbonyl]amino}-3-hydroxybutanoate

生成物 1

HCID 723379412-Tert-butoxycarbonylamino-3-difluoromethoxy-butyric acid methyl ester収率 36.1%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6342Acetonitrile溶媒3 回HCID 8857Ethyl Acetate溶媒

反応条件

温度
45 °C

実験手順

To a mixture of 2-tert-butoxycarbonylamino-3-hydroxy-butyric acid methyl ester (630 mg, 2.70 mmol) and copper(I) iodide (105 mg, 0.55 mmol) in acetonitrile at 45° C. was added a solution of 2-(fluorosulfonyl)difluoroacetic acid (0.560 mL, 5.42 mmol) in acetonitrile (2 mL) by syringe pump over 45 minutes. The reaction was then stirred at 45° C. for 30 minutes. Another solution of 2-(fluorosulfonyl)difluoroacetic acid (0.560 mL, 5.42 mmol) in acetonitrile (2 mL) was added by syringe pump over 45 minutes at 45° C. The reaction was stirred for 30 minutes at 45° C. after the second syringe pump addition was complete. Water was carefully added to quench the reaction, and the mixture was diluted with ethyl acetate. The organic layer was separated, washed with water and brine, dried (MgSO4) and concentrated. The crude material was purified by flash chromatography (10% ethyl acetate/hexanes) to yield 2-tert-butoxycarbonylamino-3-difluoromethoxy-butyric acid methyl ester (276 mg, 36%). 1H-NMR: 400 MHz, (CDCl3: 6.16 (t, JHF=74.0 Hz, 1H), 5.23-5.16 (br, 1H), 4.86-4.80 (m, 1H), 4.40 (br d, J=9.8 Hz, 1H), 3.76 (s, 3H), 1.46 (br s, 9H), 1.36 (d, J=6.4 Hz, 3H) ppm.

後処理

  1. stirringThe reaction was stirred for 30 minutes at 45° C.
  2. additionafter the second syringe pump addition
  3. customto quench
  4. customthe reaction
  5. customThe organic layer was separated
  6. washwashed with water and brine
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by flash chromatography (10% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-b2c0e32731fb4d05be3d5e24570ddc2b
出典データセット
uspto-grants-2015_10
特許番号
US09156823B2

関連ノート

読み込み中…