Hydrochloric Acid → HCID 86606435, 화합물

HRID 731010노트

반응식

HRID 731010 반응식
[C:1]([O:7][C@H:8]([CH3:13])[C:9]([O:11]C)=O)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Cl:14][CH2:15]C([O-])=O.[Na+].C(N(CC)CC)C.C([Mg]Cl)(C)(C)C.Cl>C(#N)C.C(OCC)(=O)C.O.C1COCC1>[Cl:14][CH2:15][C:9](=[O:11])[C@H:8]([O:7][C:1](=[O:6])[C:2]([CH3:3])([CH3:4])[CH3:5])[CH3:13]

참가 물질

10

반응물 5

HCID 313Hydrochloric Acid2회HCID 8471TriethylamineHCID 23665759Sodium chloroacetateHCID 71415955methyl (R)-2-pivaloyloxypropionateHCID 178418310HCID 178418310, 화합물

생성물 1

HCID 86606435HCID 86606435, 화합물수율 96.8%

시약·촉매·용매 4

HCID 962Water용매HCID 6342Acetonitrile용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

A mixture of 32.8 g (147 mmol) of methyl (R)-2-pivaloyloxypropionate, 30.5 g (261.8 mmol) of sodium chloroacetate, 26.4 g (261.55 mmol) of triethylamine, and 400 mL of THF was cooled in ice, and 299 g (523.5 mmol) of a 1.75 M solution of tert-butylmagnesium chloride was added dropwise thereto over a period of 3 hours. After the completion of the dropwise addition, the reaction was performed at 25° C. for another 2 hours, and the reaction solution was cooled in ice. A solution of 45 ml of concentrated hydrochloric acid/200 ml of water was added thereto, and subsequently 250 mL of ethyl acetate was added. Furthermore, concentrated hydrochloric acid was added for adjusting the pH to 6.0. Stirring was performed at 25° C. for 1 hour. The resulting ethyl acetate layer was separated, and 150 mL of ethyl acetate was added to the resulting aqueous layer to perform extraction again. The resulting ethyl acetate layers were combined, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 42.6 g of a crude product as an oil. A quantitative analysis was performed by HPLC. Thereby, 29.4 g of the title compound was obtained (yield: 82%, 98.7% e.e.) (HPLC, column: YMC-A302 manufactured by YMC Co. Ltd.; mobile phase: acetonitrile/20 mM (potassium) phosphate buffer solution (pH=2.5)=6/4, flow rate: 1.0 mL/min, column temperature: 30° C., detector: UV 210 nm, retention time: 5 minutes) 1H-NMR (400 MHz, CDCl3) δ: 1.25 (s, 9H), 1.46 (d, 1H, J=6.6 Hz), 4.30 (s, 2H), 5.27 (q, 1H, J=6.6 Hz).

후처리

  1. temperaturewas cooled in ice
  2. additionAfter the completion of the dropwise addition
  3. waitthe reaction was performed at 25° C. for another 2 hours
  4. temperaturethe reaction solution was cooled in ice
  5. waitwas performed at 25° C. for 1 hour
  6. customThe resulting ethyl acetate layer was separated
  7. addition150 mL of ethyl acetate was added to the resulting aqueous layer
  8. extractionextraction again
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated under reduced pressure
  11. customto obtain 42.6 g of a crude product as an oil

출처 및 근거

ORD 기록
ord-9c50ccadd8454323a2802036e6f12c73
출처 데이터셋
uspto-grants-2009_09
특허 번호
US07582781B2

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