1,2-Dichloroethane → 1-[2-(4-Methoxy-benzoylamino)-2-methyl-propionyl]-pyrrolidine-2-carboxylic acid (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-amide

HRID 900570

반응식

HRID 900570 반응식
C(O[C:5](=[O:21])[NH:6][CH:7]1[CH2:11][C:10](=[O:12])[O:9][CH:8]1[O:13][CH2:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)C=C.CC1C2C(=CC=CC=2)C(C)=C2C=1C=CC1C2=CC=CC=1.[CH3:42][O:43][C:44]1[CH:65]=[CH:64][C:47]([C:48]([NH:50][C:51]([CH3:63])([CH3:62])[C:52]([N:54]2[CH2:58][CH2:57][CH2:56][CH:55]2C(O)=O)=[O:53])=[O:49])=[CH:46][CH:45]=1.C1C=CC2N(O)N=NC=2C=1.C(Cl)CCl>C(Cl)Cl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:14]([O:13][CH:8]1[CH:7]([NH:6][C:5]([CH:55]2[CH2:56][CH2:57][CH2:58][N:54]2[C:52](=[O:53])[C:51]([NH:50][C:48](=[O:49])[C:47]2[CH:46]=[CH:45][C:44]([O:43][CH3:42])=[CH:65][CH:64]=2)([CH3:63])[CH3:62])=[O:21])[CH2:11][C:10](=[O:12])[O:9]1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

참가 물질

8

반응물 5

HCID 111,2-DichloroethaneHCID 60017,12-Dimethylbenz(a)anthraceneHCID 757711-HydroxybenzotriazoleHCID 186236811-[2-(4-Methoxy-benzoylamino)-2-methyl-propionyl]-pyrrolidine-2-carboxylic acidHCID 22321532(2-Benzyloxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester

생성물 1

HCID 229777781-[2-(4-Methoxy-benzoylamino)-2-methyl-propionyl]-pyrrolidine-2-carboxylic acid (2-benzyloxy-5-oxo-tetrahydro-furan-3-yl)-amide수율 61%

시약·촉매·용매 2

HCID 178418397HCID 178418397, 화합물촉매HCID 6344Dichloromethane용매2회

실험 절차

To a solution of (2-benzyloxy-5-oxo-tetrahydrofuran-3-yl)-carbamic acid allyl ester (40) (1.027 g, 3.5 mmol) in CH2Cl2 (20 ml) was added DMBA (543 mg, 3.48 mmol) and Pd(PPh3)4 (280 mg, 0.24 mmol) and the solution was stirred at room temperature under N2 for 20 minutes. A solution of 1-[2-(4-methoxy-benzoylamino)-2-methyl-propionyl]-pyrrolidine-2-carboxylic acid (818 mg, 2.45 mmol) in CH2Cl2 (5 ml) was added, followed by HOBT (0.534 g, 3.95 mmol) and EDC (738 mg, 3.84 mmol). The reaction was stirred at room temperature for 18 hours under N2. The solvent was evaporated, the crude material dissolved in EtOAc and washed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine and was dried over anhydrous Na2SO4, filtered and evaporated to give a yellow solid. Purification by flash column chromatography, eluting with ethyl acetate/hexanes (20/80 to 50/50%), gave the product as pale yellow solid (760 mg, 61% yield). 1H-NMR (500 MHz, CD3OD) δ 1.53 (d, 6H), 1.65-1.93 (m, 3H), 1.96-2.14 (m, 1H), 2.60 (dd, 0.1H), 2.77 (dd, 0.85H), 2.94 (dd, 0.85H), 3.04-3.11 (m, 0.2H), 3.42-3.52 (m, 1H), 3.57-3.67 (m, 1H), 3.84 (s, 3H), 4.38-4.76 (m, 3H), 4.84 (d, 1H), 5.64-5.70 (m, 1H), 6.96-7.03 (m, 2H), 7.23-7.43 (m, 5H), 7.78-7.97 (m, 2H). Analytical HPLC (C18 column) 13.32, 14.37 min. LC-MS (ES+) m/e=524.3 (M+H).

후처리

  1. stirringThe reaction was stirred at room temperature for 18 hours under N2
  2. customThe solvent was evaporated
  3. dissolutionthe crude material dissolved in EtOAc
  4. washwashed with 0.5N NaHSO4 (2×), saturated NaHCO3 (2×) and brine
  5. dry with materialwas dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. customevaporated
  8. customto give a yellow solid
  9. customPurification by flash column chromatography
  10. washeluting with ethyl acetate/hexanes (20/80 to 50/50%)

출처 및 근거

ORD 기록
ord-6e5e112231df4befa6eeb52aa3451e83
출처 데이터셋
uspto-grants-2008_04
특허 번호
US07358273B2

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