4-Methylmorpholine → tert-butyl (2S,4EZ)-2-({[(2S)-2-hydroxy-2-phenylethyl]amino}carbonyl)-4-(methoxyimino)-1-pyrrolidine-carboxylate

HRID 1349012

반응식

HRID 1349012 반응식
[C:1]([O:5][C:6]([N:8]1[CH2:12][C:11](=[N:13][O:14][CH3:15])[CH2:10][C@H:9]1[C:16]([OH:18])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.[NH2:34][CH2:35][C@H:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[OH:37]>C1COCC1>[OH:37][C@@H:36]([C:38]1[CH:43]=[CH:42][CH:41]=[CH:40][CH:39]=1)[CH2:35][NH:34][C:16]([C@@H:9]1[CH2:10][C:11](=[N:13][O:14][CH3:15])[CH2:12][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:18]

참가 물질

6

반응물 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 643217(1S)-2-amino-1-phenylethan-1-olHCID 58714586(2S,4EZ)-1(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid2회

생성물 1

HCID 131725396tert-butyl (2S,4EZ)-2-({[(2S)-2-hydroxy-2-phenylethyl]amino}carbonyl)-4-(methoxyimino)-1-pyrrolidine-carboxylate수율 96%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매

반응 조건

온도
-25 °C

실험 절차

To a solution of the central building block, e.g. (2S,4EZ)-1-(tert-butoxycarbonyl)-4-(methoxyimino)-2-pyrrolidinecarboxylic acid (Intermediate 7) (24.2 mmol, 6.24 g) in dry THF (125 ml) at −25° C. was added NMM (2.5 eq, 60.4 mmol, 6.64 ml) followed by isobutylchloroformate (1.05 eq, 25.4 mmol, 3.3 ml). The resulting mixture was stirred at −25° C. for 30 min and an amine or an amine salt, e.g. (S)-2-amino-1-phenylethanol (1.51 eq, 36.5 mmol, 5 g) was then added. The mixture was allowed to gradually warm to rt. After 16 h, the solvents were removed. The residue was dissolved in AcOEt, washed twice with NH4Cl saturated solution, then twice with 10% NaHCO3 solution. The organic layer was dried over Na2SO4, filtrated and concentrated to afford the desired product, e.g. tert-butyl (2S,4EZ)-2-({[(2S)-2-hydroxy-2-phenylethyl]amino}carbonyl)-4-(methoxyimino)-1-pyrrolidine-carboxylate (8.76 g, 96%) as a pale yellow oil in 88.5% purity by HPLC.

후처리

  1. temperatureto gradually warm to rt
  2. waitAfter 16 h
  3. customthe solvents were removed
  4. dissolutionThe residue was dissolved in AcOEt
  5. washwashed twice with NH4Cl saturated solution
  6. dry with materialThe organic layer was dried over Na2SO4
  7. filtrationfiltrated
  8. concentrationconcentrated

출처 및 근거

ORD 기록
ord-38e99fb90d0a44f28a544fa0260120f7
출처 데이터셋
uspto-grants-2007_05
특허 번호
US07211601B2

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