4-Methylmorpholine → (2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 1674520

반응식

HRID 1674520 반응식
[CH3:1][C:2]([O:5][C:6]([N:8]1[C@H:12]([C:13]([OH:15])=O)[CH2:11][CH:10]([OH:16])[CH2:9]1)=[O:7])([CH3:4])[CH3:3].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl.[NH2:49][C@:50]1([C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:52][C@H:51]1[CH:53]=[CH2:54]>C(Cl)Cl.[Au]>[C:2]([O:5][C:6]([N:8]1[CH2:9][C@H:10]([OH:16])[CH2:11][C@H:12]1[C:13]([NH:49][C@:50]1([C:55]([O:57][CH2:58][CH3:59])=[O:56])[CH2:52][C@H:51]1[CH:53]=[CH2:54])=[O:15])=[O:7])([CH3:1])([CH3:3])[CH3:4]

참가 물질

7

반응물 4

HCID 79724-MethylmorpholineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 111389801-(1,1-Dimethylethyl) (2S)-4-hydroxy-1,2-pyrrolidinedicarboxylateHCID 66670028Cyclopropanecarboxylic acid, 1-amino-2-ethenyl-, ethyl ester, hydrochloride (1:1), (1R,2S)-

생성물 1

HCID 57892908(2S,4R)-tert-butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate수율 94%

시약·촉매·용매 2

HCID 23985Gold촉매HCID 6344Dichloromethane용매

실험 절차

A stirred slurry of Boc-L-4-hydroxyproline (N-Boc (2S,4R)-hydroxyproline) (10 g, 43.3 mmol) in 400 mL of methylene chloride was treated sequentially with N-methyl morpholine (9.3 mL, 84.7 mmol), HATU (19.5 g, 51.3 mmol), and ethyl 1(R)-amino-2(S)-vinylcyclopropanecarboxylate hydrochloride (9.1 g, 47.5 mmol). The gold homogeneous solution was stirred at rt under N2 for 18 h, and then concentrated in vacuo to give a brown oil. This was partitioned between ethyl acetate and sat. aq. NaHCO3. The organic phase was washed with brine, dried (MgSO4), and concentrated in vacuo to give 15 g (94%) of ethyl 1(R)-[1-tert-butoxycarbonyl-4(R)-hydroxypyrrolidine-2(S)-carboxamido]-2(S)-vinylcyclopropanecarboxylate as a off-white solid: LC-MS (Xterra HPLC column: 3.0×50 mm length. Gradient: 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B. Gradient time: 3 min. Hold time: 1 min. Flow rate: 5 mL/min. Detector Wavelength: 220 nM. Solvent A: 10% MeOH/90% H2O/0.1% TFA. Solvent B: 10% H2O/90% MeOH/0.1% TFA.) (Retention time: 2.09 min), MS m/z 369 (M++1).

후처리

  1. concentrationconcentrated in vacuo
  2. customto give a brown oil
  3. customThis was partitioned between ethyl acetate and sat. aq. NaHCO3
  4. washThe organic phase was washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated in vacuo

출처 및 근거

ORD 기록
ord-40b5e8205a4d432fa1d1247fd25bd98e
출처 데이터셋
uspto-grants-2011_08
특허 번호
US08003604B2

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