1,2-Dichloroethane → HCID 9892498, 화합물

HRID 2215970노트

반응식

HRID 2215970 반응식
C([O:8][C:9](=O)[NH:10][CH:11]([C:16]([N:18]1[CH2:22][CH2:21][CH2:20][CH:19]1[C:23](=[O:34])[NH:24][CH:25]1[CH2:29][C:28](=[O:30])[O:27][CH:26]1[O:31][CH2:32][CH3:33])=[O:17])[C:12]([CH3:15])([CH3:14])[CH3:13])C1C=CC=CC=1.[H][H].[NH2:38][C:39]1[CH:47]=[CH:46][C:42](C(O)=O)=[CH:41][C:40]=1[Cl:48].C(Cl)CCl.C(N(C(C)C)CC)(C)C>C(O)C.C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[CH2:32]([O:31][CH:26]1[CH:25]([NH:24][C:23]([CH:19]2[CH2:20][CH2:21][CH2:22][N:18]2[C:16](=[O:17])[CH:11]([NH:10][C:9](=[O:8])[C:42]2[CH:46]=[CH:47][C:39]([NH2:38])=[C:40]([Cl:48])[CH:41]=2)[C:12]([CH3:13])([CH3:15])[CH3:14])=[O:34])[CH2:29][C:28](=[O:30])[O:27]1)[CH3:33]

참가 물질

9

반응물 5

HCID 111,2-DichloroethaneHCID 172114-Amino-3-chlorobenzoic acidHCID 81531DiisopropylethylamineHCID 59730815Benzyl (S)-1-((S)-2-((2R,3S)-2-ethoxy-5-oxotetrahydrofuran-3-ylcarbamoyl)-pyrrolidin-1-yl)-3,3-dimethyl-1-oxobutan-2-ylcarbamateHCID 178418361HCID 178418361, 화합물

생성물 1

HCID 9892498HCID 9892498, 화합물수율 65.5%

시약·촉매·용매 3

HCID 9942167Palladium hydroxide촉매HCID 702Ethanol용매HCID 8857Ethyl Acetate용매

실험 절차

A solution of {1-[2-(2-ethoxy-5-oxo-tetrahydrofuran-3-yl carbamoyl)-pyrrolidine-1-carbonyl]-2,2-dimethylpropyl}carbamic acid benzyl ester (0.12 g, 0.24 mmol) in ethanol (5 mL) was treated with 10% palladium hydroxide on carbon (0.05 g), was stirred under 1 atm hydrogen pressure for 4 h, was filtered through Celite and was evaporated. The crude intermediate was dissolved in dichloromethane (5 mL), and was treated with 4-amino-3-chlorobenzoic acid (0.04 g, 0.26 mmol), EDC (0.06 g, 0.29 mmol) and diisopropylethylamine (0.13 mL, 0.71 mmol) and was stirred at room temperature under nitrogen for 20 h. The reaction was diluted with ethyl acetate, was washed with 10% potassium bisulfate, saturated sodium bicarbonate and brine, was dried (sodium sulfate) and was evaporated. Purification by flash chromatography (SiO2) eluted with 7:3 ethyl acetate hexanes provided 1-[2-(4-amino-3-chlorobenzoylamino)-3,3-dimethylbutyryl]pyrrolidine-2-carboxylic acid (2-ethoxy-5-oxo-tetrahydrofuran-3-yl)amide (0.08 g, 62% yield) as a colorless film. 1H-NMR (500 MHz, CDCl3) d 7.67 (d, J=2.0 Hz, 1H), 7.50 (m, 0.2H), 7.44 (dd, J=8.4, 2.0 Hz, 1.0H), 7.33 (d, J=8.0 Hz, 0.8H), 6.69 (d, J=8.4 Hz, 1H), 6.55 (d, J=9.2 Hz, 1H), 5.39 (d, J=5.2 Hz, 0.8H), 5.29 (s, 0.2H), 4.79 (d, J=9.4 Hz, 1H), 4.62 (m, 0.8H), 4.50 (m, 1.0H), 4.25 (m, 0.2H), 3.83 (m, 0.8H), 3.77 (m, 0.2H), 3.62 (m, 0.8H), 3.55 (m, 0.2H), 2.92 (m, 0.2H), 2.76 (dd, J=17.2, 8.4 Hz, 0.8H), 2.30 (m, 2H), 2.05 (m, 1H), 1.93 (m, 1.0H), 1.85 (m, 1H), 1.22 (t, J=7.1 Hz, 2.4H), 1.16 (t, J=7.1 Hz, 0.6H), 1.00 (s, 9H) ppm. 1H-NMR shows ˜8:2 syn:anti epimers. LC/MS (ES+): m/e=509.08 (M+H).

후처리

  1. filtrationwas filtered through Celite
  2. customwas evaporated
  3. dissolutionThe crude intermediate was dissolved in dichloromethane (5 mL)
  4. washwas washed with 10% potassium bisulfate, saturated sodium bicarbonate and brine
  5. dry with materialwas dried (sodium sulfate)
  6. customwas evaporated
  7. customPurification by flash chromatography (SiO2)
  8. washeluted with 7:3 ethyl acetate hexanes

출처 및 근거

ORD 기록
ord-7adf68368a30426aa0c7c24bbe8edf4f
출처 데이터셋
uspto-grants-2006_09
특허 번호
US07109357B2

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