Diisopropylamine → Atreleuton

HRID 52177

반응식

HRID 52177 반응식
[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

참가 물질

10

반응물 4

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

생성물 1

HCID 3086671Atreleuton수율 64%

시약·촉매·용매 5

HCID 11776Triphenylphosphine촉매HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)촉매HCID 6093782Bis(acetonitrile)dichloropalladium촉매HCID 7915Isopropyl Acetate용매HCID 8900Heptane용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5056873437f64447b31b2631be516faa
출처 데이터셋
uspto-grants-1997_04
특허 번호
US05616596

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