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

HRID 1797778

反応式

HRID 1797778 の反応式
[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]

参加物

7

反応物 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)-

生成物 1

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

試薬・触媒・溶媒 2

HCID 23985Gold触媒HCID 6344Dichloromethane溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-91b85fe898eb48f7b3f01981bb9aa5c4
出典データセット
uspto-grants-2013_01
特許番号
US08343477B2

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