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

HRID 1751355노트

반응식

HRID 1751355 반응식
[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]

참가 물질

7

반응물 3

HCID 962WaterHCID 27375162,2-Difluoro-2-(fluorosulfonyl)acetic acid2회HCID 4351132Methyl 2-{[(tert-butoxy)carbonyl]amino}-3-hydroxybutanoate

생성물 1

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

시약·촉매·용매 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6342Acetonitrile용매3회HCID 8857Ethyl Acetate용매

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온도
45 °C

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-b2c0e32731fb4d05be3d5e24570ddc2b
출처 데이터셋
uspto-grants-2015_10
특허 번호
US09156823B2

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