Hydrochloric Acid → N-(Methoxycarbonyl)-O-methyl-L-homoserine

HRID 1809322

반응식

HRID 1809322 반응식
[NH:1]1CCCCC1.[CH3:7][O:8][CH2:9][CH2:10][CH2:11][C:12]([OH:14])=[O:13].C([O-])([O-])=O.[Na+].[Na+].Cl[C:22]([O:24][CH3:25])=[O:23].Cl>CN(C=O)C>[CH3:7][O:8][CH2:9][CH2:10][C@H:11]([NH:1][C:22]([O:24][CH3:25])=[O:23])[C:12]([OH:14])=[O:13]

참가 물질

7

반응물 5

HCID 313Hydrochloric AcidHCID 6586Methyl chloroformateHCID 8082PiperidineHCID 10340Sodium CarbonateHCID 922644-Methoxybutyric acid

생성물 1

HCID 59610349N-(Methoxycarbonyl)-O-methyl-L-homoserine수율 47.9%

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

실험 절차

Piperidine (1.0 mL, 10 mmol) was added to a solution of (S)-2-(9H-fluoren-9-yl)methoxy)carbonylamino)-4-methoxybutanoic acid (0.355 g, 1 mmol) in DMF (3 mL), and the mixture was stirred at rt for 3 h. The volatiles were removed and the residue was partitioned between sat. NaHCO3 (aq.) (5 mL) and EtOAc (5 mL). The aqueous layer was further washed with EtOAc and Et2O. To the aqueous solution was added Na2CO3 (212 mg, 2.0 mmol) followed by methyl chloroformate (0.16 mL, 2.0 mmol) and the reaction mixture was stirred at rt for 16 h. The reaction mixture was acidified with 1 N HCl (aq.) until pH<7 and then extracted with EtOAc (2×10 mL). The combined organic layers were dried (Na2SO4), filtered and concentrated. The residue was purified by flash silica chromatography (EtOAc/hexanes, gradient from 20% to 70%) to yield (S)-4-methoxy-2-(methoxycarbonylamino)butanoic acid (Cap-194) (91.5 mg) as viscous colorless oil. LC-MS retention time=0.61 min; m/z 214 [M+Na]+. (Column: PHENOMENEX® Luna 3.0×50 mm S10. Solvent A=90% Water: 10% Methanol: 0.1% TFA. Solvent B=10% Water: 90% Methanol: 0.1% TFA. Flow Rate=4 mL/min. Start % B=0. Final % B=100. Gradient Time=3 min. Wavelength=220). 1H NMR (400 MHz, chloroform-d) δ ppm 7.41 (br. s., 1H), 5.74-6.02 (m, 1H), 4.32-4.56 (m, 1H), 3.70 (s, 3H), 3.54 (t, J=5.0 Hz, 2H), 3.34 (s, 3H), 1.99-2.23 (m, 2H).

후처리

  1. customThe volatiles were removed
  2. customthe residue was partitioned between sat. NaHCO3 (aq.) (5 mL) and EtOAc (5 mL)
  3. washThe aqueous layer was further washed with EtOAc and Et2O
  4. stirringthe reaction mixture was stirred at rt for 16 h
  5. extractionextracted with EtOAc (2×10 mL)
  6. dry with materialThe combined organic layers were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe residue was purified by flash silica chromatography (EtOAc/hexanes, gradient from 20% to 70%)

출처 및 근거

ORD 기록
ord-83d1c6303fb64e479664a95cceb3575e
출처 데이터셋
uspto-grants-2013_01
특허 번호
US08362020B2

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