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

HRID 73134

反応式

HRID 73134 の反応式
[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]

参加物

10

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 178418476HCID 178418476、化合物触媒HCID 679Dimethyl Sulfoxide溶媒HCID 3283Diethyl Ether溶媒HCID 8857Ethyl Acetate溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-7b18b60943de4f2fa8356471fd90c14d
出典データセット
uspto-grants-2014_09
特許番号
US08829033B2

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