Ethyl iodoacetate → Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate

HRID 2402140ノート

反応式

HRID 2402140 の反応式
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([CH2:13][CH:14]=[CH2:15])[C:10](Cl)=O)[CH:5]=[CH:6][C:7]=1[Cl:8].[N:16]1([C:22](=[S:26])[CH2:23][C:24]#[N:25])[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1.C(N(CC)C(C)C)(C)C.I[CH2:37][C:38]([O:40][CH2:41][CH3:42])=[O:39]>C(#N)C>[C:24]([C:23]1[C:10]([CH:9]([C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=2)[CH2:13][CH:14]=[CH2:15])=[C:37]([C:38]([O:40][CH2:41][CH3:42])=[O:39])[S:26][C:22]=1[N:16]1[CH2:21][CH2:20][O:19][CH2:18][CH2:17]1)#[N:25]

参加物

6

反応物 4

HCID 12183Ethyl iodoacetateHCID 81531Diisopropylethylamine2 回HCID 221772412-(3,4-Dichlorophenyl)pent-4-enoyl chlorideHCID 451589413-Morpholin-4-yl-3-thioxopropanenitrile

生成物 1

HCID 68006701Ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate収率 15.9%

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒

実験手順

To a solution of 2-(3,4-dichlorophenyl)pent-4-enoyl chloride (2.51 g, 9.53 mmol) and 3-morpholin-4-yl-3-thioxopropanenitrile (1.62 g, 9.53 mmol) in acetonitrile (40.0 mL) in a 100 mL round bottom flask was added N,N-diisopropylethylamine (1.82 mL, 10.5 mmol), and the resulting deep orange/red solution was stirred at room temp for 1 hr. To the resulting mixture was added N,N-diisopropylethylamine (4.15 mL, 23.8 mmol) and then ethyl iodoacetate (1.24 mL, 10.5 mmol). The flask was fitted with a reflux condenser and the reaction was heated to reflux over 48 hrs. The mixture was concentrated and distributed between NaHCO3(aq) saturated solution and EtOAc. The aqueous layer was extracted with EtOAc (×2). The combined org layer was washed with brine, dried, and concentrated to provide a dark syrup. Purification on a silica gel column (gradient elution 3-30% EtOAc/hexanes) provided ethyl 4-cyano-3-[1-(3,4-dichlorophenyl)but-3-en-1-yl]-5-(morpholin-4-yl)thiophene-2-carboxylate (704 mg, 15.9% yield). LCMS: (AA) ES+ 465, 467, 469; 1H NMR (400 MHz, CDCl3) δ 7.49-7.42 (m, 1H), 7.41-7.33 (m, 1H), 7.31-7.27 (m, 1H), 5.82-5.66 (ddt, J=17.2, 10.1, 6.8 Hz, 1H), 5.62-5.50 (t, J=8.2 Hz, 1H), 5.16-5.08 (dd, J=17.1, 1.6 Hz, 1H), 5.04-4.94 (dd, J=10.2, 1.5 Hz, 1H), 4.35-4.27 (q, J=7.1 Hz, 2H), 3.86-3.78 (m, 4H), 3.59-3.48 (m, 4H), 3.10-2.99 (h, J=6.9 Hz, 2H), 1.40-1.31 (m, 3H).

後処理

  1. customThe flask was fitted with a reflux condenser
  2. temperaturethe reaction was heated
  3. temperatureto reflux over 48 hrs
  4. concentrationThe mixture was concentrated
  5. extractionThe aqueous layer was extracted with EtOAc (×2)
  6. washThe combined org layer was washed with brine
  7. customdried
  8. concentrationconcentrated
  9. customto provide a dark syrup
  10. customPurification
  11. washon a silica gel column (gradient elution 3-30% EtOAc/hexanes)

出典と根拠

ORDレコード
ord-87eaf093e7e04900bf6d47ea85452858
出典データセット
uspto-grants-2014_08
特許番号
US08796271B2

反応ノート

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