Diethylamine → Atreleuton

HRID 1720435

反応式

HRID 1720435 の反応式
I[C:2]1[S:3][C:4]([CH2:7][C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)=[CH:5][CH:6]=1.[OH:15][N:16]([C@@H:20]([C:22]#[CH:23])[CH3:21])[C:17]([NH2:19])=[O:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(NCC)C>CN(C=O)C.CC#N.CC#N.Cl[Pd]Cl.[Cu]I>[F:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][C:4]2[S:3][C:2]([C:23]#[C:22][C@H:20]([N:16]([OH:15])[C:17]([NH2:19])=[O:18])[CH3:21])=[CH:6][CH:5]=2)=[CH:9][CH:10]=1

参加物

8

反応物 4

HCID 8021DiethylamineHCID 11776TriphenylphosphineHCID 10558641(R)-N-hydroxy-N-(3-butyn-2-yl)ureaHCID 106154672-(4-Fluorobenzyl)-5-iodothiophene

生成物 1

HCID 3086671Atreleuton収率 18%

試薬・触媒・溶媒 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6093782Bis(acetonitrile)dichloropalladium触媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (5.30 g, 16.6 mmol), prepared as in step 2, in anhydrous DMF (5.0 mL) was added (R)-N-hydroxy-N-(3-butyn-2-yl)urea (2.12 g, 16.6 mmol), triphenylphosphine (84 mg, 0.32 mmol), bis(acetonitrile)palladium(II) chloride (40 mg, 0.16 mmol), copper (I) iodide (16 rag, 0.08 mmol), and diethylamine (5.6 ml). The mixture was stirred under nitrogen at ambient temperature for 22 hours and concentrated in vacuo at 32° C. The residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2 to afford (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl}-N-hydroxyurea as a cream-colored solid 0.94 g (18%). m.p. 135°-136° C.(dec). 1H NMR (DMSO-d6, 300 MHz) δ1.32 (d, J=6.0 Hz, 3H), 4.11 (s, 2H), 5.10 (q, J=6.0Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0Hz, 1H), 7.08 (d, J=3.0Hz, 1H), 7.10-7.18 (m, 2H), 7.25-7.32 (m, 2H), 9.33 (s, 1H). MS (DCI/NH3) m/e 319 (M+H)+. [a]D23° =+47.8° (C=1, MeOH). Anal calcd for C16H15FN2O2S: C, 60.36; H, 4.75; N, 8.80. Found: C, 60.31; H, 4.79; N, 8.50.

後処理

  1. concentrationconcentrated in vacuo at 32° C
  2. customThe residue was subjected to chromatography on silica eluting with 2-7% MeOH in CH2Cl2, crystallization from ethyl acetate-hexane and trituration in CH2Cl2

出典と根拠

ORDレコード
ord-b542e964429c4fb68f9b84c4a70fad81
出典データセット
uspto-grants-1996_04
特許番号
US05506261

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