Tetrahydrofuran → (R)-2-Acetamido-3-methoxy-N-(4-(3-methoxyprop-1-ynyl)benzyl)propanamide

HRID 73134

반응식

HRID 73134 반응식
[CH2:1]1[CH2:5][O:4][CH2:3][CH2:2]1.[C:6]([NH:9][C@H:10]([CH2:22][O:23][CH3:24])[C:11]([NH:13][CH2:14][C:15]1[CH:20]=[CH:19][C:18](I)=[CH:17][CH:16]=1)=[O:12])(=[O:8])[CH3:7].C(N(CC)CC)C.COCC#C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I.CS(C)=O.CCOC(C)=O.CCOCC>[C:6]([NH:9][C@H:10]([CH2:22][O:23][CH3:24])[C:11]([NH:13][CH2:14][C:15]1[CH:16]=[CH:17][C:18]([C:2]#[C:1][CH2:5][O:4][CH3:3])=[CH:19][CH:20]=1)=[O:12])(=[O:8])[CH3:7]

참가 물질

10

반응물 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 693933-MethoxypropyneHCID 45486399(R)-2-acetamido-3-methoxy-N-(4-iodobenzyl)propanamide

생성물 1

HCID 44538056(R)-2-Acetamido-3-methoxy-N-(4-(3-methoxyprop-1-ynyl)benzyl)propanamide

시약·촉매·용매 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 178418476HCID 178418476, 화합물촉매HCID 679Dimethyl Sulfoxide용매HCID 3283Diethyl Ether용매HCID 8857Ethyl Acetate용매

실험 절차

To an anhydrous THF (10 mL) solution of (R)-2-acetamido-3-methoxy-N-(4-iodobenzyl)propanamide (376 mg, 1.0 mmol), triethylamine (280 μL, 2.0 mmol), 3-methoxyprop-1-yne (125 μl, 1.5 mmol), dichlorobis(triphenylphosphine)-palladium (II) (70 mg, 0.1 mmol), and CuI (38 mg, 0.2 mmol) were sequentially added under Ar. The mixture was stirred at room temperature (4 h), and then Et2O (10 mL) added and the precipitate filtered through a Celite pad. The filtrate was concentrated in vacuo and the residue was purified by flash chromatography on silica gel with EtOAc/MeOH (9/1) as the eluant to obtain (R)-6 (260 mg, 82%) as a beige solid: Rf=0.27 (EtOAc); mp 141-142° C.; [α]27D=+ 4.4° (c 1, DMSO); IR (nujol) 3278, 3096, 1640, 1554, 1458, 1370, 1304, 1257, 1192, 1099, 966, 903, 810, 732 cm−1; 1H NMR (CDCl3) δ 2.02 (s, CH3CO), 3.37 (s, OCH3), 3.45-3.47 (m, CHH′ and OCH3), 3.78 (dd, J=4.2, 9.0 Hz, CHH′), 4.32 (s, C≡CCH2OCH3) 4.38-4.52 (m, CH2N), 4.54-4.61 (m, NC(H)CO), 6.52 (d, J=6.6 Hz, CHNH), 6.91-6.99 (br t, CH2NH), 7.19 (d, J=7.9 Hz, 2 ArH), 7.41 (d, J=7.9 Hz, 2 ArH); 13C NMR (CDCl3) δ 23.2 (CH3CO), 43.2 (CH2N), 52.5 (CHCH2), 57.7 (C≡CCH2OCH3), 59.1 (OCH3), 60.4 (C≡CCH2OCH3), 71.7 (CH2OCH3), 85.2 (C≡C), 86.0 (C≡C), 121.8, 127.3, 132.1, 138.4 (C6H4), 170.4 (2C(O)); HRMS (M+H+) (ESI+) 319.1652 [M+H+] (calcd for C17H22N2O4H+ 319.1658); Anal. Calcd. for C17H22N2O4.0.33H2O: C, 62.95; H, 7.04; N, 8.64. Found: C, 62.98; H, 6.78; N, 8.47.

후처리

  1. filtrationthe precipitate filtered through a Celite pad
  2. concentrationThe filtrate was concentrated in vacuo
  3. customthe residue was purified by flash chromatography on silica gel with EtOAc/MeOH (9/1) as the eluant
  4. customto obtain (R)-6 (260 mg, 82%) as a beige solid

출처 및 근거

ORD 기록
ord-7b18b60943de4f2fa8356471fd90c14d
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08829033B2

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