Diisopropylamine → Atreleuton

HRID 52177

反応式

HRID 52177 の反応式
[OH:1][N:2]([C@@H:6]([C:8]#[CH:9])[CH3:7])[C:3]([NH2:5])=[O:4].I[C:11]1[S:12][C:13]([CH2:16][C:17]2[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=2)=[CH:14][CH:15]=1.C(NC(C)C)(C)C.[NH4+].[OH-]>C(OC(=O)C)(C)C.CC#N.CC#N.Cl[Pd]Cl.[Cu]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCCCCC>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH2:16][C:13]2[S:12][C:11]([C:9]#[C:8][C@H:6]([N:2]([OH:1])[C:3]([NH2:5])=[O:4])[CH3:7])=[CH:15][CH:14]=2)=[CH:18][CH:19]=1

参加物

10

反応物 4

HCID 7912DiisopropylamineHCID 14923Ammonium HydroxideHCID 10558641(R)-N-hydroxy-N-(3-butyn-2-yl)ureaHCID 106154672-(4-Fluorobenzyl)-5-iodothiophene

生成物 1

HCID 3086671Atreleuton収率 64%

試薬・触媒・溶媒 5

HCID 11776Triphenylphosphine触媒HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 6093782Bis(acetonitrile)dichloropalladium触媒HCID 7915Isopropyl Acetate溶媒HCID 8900Heptane溶媒

実験手順

To the (R)-N-hydroxy-N-(3-butyn-2-yl)urea prepared in step 3 above was added a solution of 2-iodo-5-(4-fluorophenylmethyl)thiophene (45 mmol), in isopropylacetate, followed by diisopropylamine (10 mL, 7.2 g, 71 mmol), bis(acetonitrile)palladium(II) chloride (65 mg, 0.25 mmol), copper(I)iodide (95 mg, 0.50 mmol), and triphenylphosphine (131 mg, 0.50 mmol), and the reaction mixture was stirred under nitrogen at ambient temperature for 2 hours. The reaction mixture was poured into 20% aqueous NH4OH (200 mL) and stirred for 20 min. Heptane (300 mL) was added and the mixture was cooled in an ice-water bath and stirred for 15 min. The solid was filtered off, washed with H2O, heptane, 25% CH2Cl2 /heptane, and dried in vauco to give 10.2 g (64% yield from (S)-O-p-toluenesulfonyl-3-butyn-2-ol) of (R)-N-{3-[5-(4-fluorophenylmethyl)thien-2-yl]-1-methyl-2-propynyl)-N-hydroxyurea (98% ee by chiral HPLC). 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=6.0 Hz, 1H), 6.54 (s, 2H), 6.81 (d, J=3.0 Hz, 1H), 7.08 (d, J=3.0 Hz, 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)+. [α]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. stirringstirred for 20 min
  2. temperaturethe mixture was cooled in an ice-water bath
  3. stirringstirred for 15 min
  4. filtrationThe solid was filtered off
  5. washwashed with H2O, heptane, 25% CH2Cl2 /heptane
  6. customdried in vauco

出典と根拠

ORDレコード
ord-5056873437f64447b31b2631be516faa
出典データセット
uspto-grants-1997_04
特許番号
US05616596

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