Methyl iodide → N-((1R)-1-(Methoxymethyl)-3-methylbutyl)-3,4-dimethylbenzamide

HRID 1518579ノート

反応式

HRID 1518579 の反応式
[OH:1][CH2:2][C@H:3]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=1)[CH2:4][CH:5]([CH3:7])[CH3:6].[OH-].[Na+].I[CH3:22]>CN(C=O)C>[CH3:22][O:1][CH2:2][C@H:3]([NH:8][C:9](=[O:18])[C:10]1[CH:15]=[CH:14][C:13]([CH3:16])=[C:12]([CH3:17])[CH:11]=1)[CH2:4][CH:5]([CH3:7])[CH3:6]

参加物

5

反応物 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 39352414(R)-N-(1-hydroxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide

生成物 1

HCID 57527964N-((1R)-1-(Methoxymethyl)-3-methylbutyl)-3,4-dimethylbenzamide収率 73.1%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒2 回

反応条件

温度
0 °C

実験手順

To a solution of (R)—N-(1-hydroxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide (1.59 g, 6.39 mmol) (example 18a) in dry DMF (20 mL) was added powdered NaOH (281 mg, 7 mmol) an the solution was stirred at 0° C. for 2 hrs. Iodomethane (1 eq, 6.39 mmol) was added in DMF (10 ml) drop-wise over period of 1 hr. The temperature was kept at 0° C. and the mixture was stirred for 1 hr. The reaction was quenched by adding 300 ml of water. The aqueous layer was extracted with dichloromethane, dried over MgSO4 and evaporated. The residue was purified by flash chromatography on silica-gel (toluene-ethyl acetate; 5-20% gradient) to give 1.23 g (R)—N-(1-methoxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide (73%). 1H NMR (500 MHz, CDCl3): ÿ 0.94-0.97 (t, 6H), 1.41-1.47 (M, 1H), 1.54-1.60 (m, 1H), 1.64-1.68 (m, 1H), 2.29 (d, 6H)5 3.36 (s3 3H), 3.45-3.50 (m, 2H), 4.34-4.39 (m, 1H), 6.23-6.25 (d, 1H), 7.16-7.17 (d, 1H), 7.47-7.49 (dd, 1H), 7.56 (s, 1H). MS (M+H, 264.3).

後処理

  1. customwas kept at 0° C.
  2. stirringthe mixture was stirred for 1 hr
  3. customThe reaction was quenched
  4. additionby adding 300 ml of water
  5. extractionThe aqueous layer was extracted with dichloromethane
  6. dry with materialdried over MgSO4
  7. customevaporated
  8. customThe residue was purified by flash chromatography on silica-gel (toluene-ethyl acetate; 5-20% gradient)

出典と根拠

ORDレコード
ord-d8ac853d844343e685bc2012bfa918a8
出典データセット
uspto-grants-2015_07
特許番号
US09072313B2

反応ノート

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