Chloromethyl Methyl Ether → (R)-N-(1-(methoxymethoxy)-4-methylpentan-2-yl)-3,4-dimethylbenzamide

HRID 1644068ノート

反応式

HRID 1644068 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+].Cl[CH2:22][O:23][CH3:24]>CN(C=O)C>[CH3:22][O:23][CH2:24][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 7864Chloromethyl Methyl EtherHCID 14798Sodium HydroxideHCID 39352414(R)-N-(1-hydroxy-4-methylpentan-2-yl)-3,4-dimethylbenzamide

生成物 1

HCID 57527952(R)-N-(1-(methoxymethoxy)-4-methylpentan-2-yl)-3,4-dimethylbenzamide収率 53%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

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 (Example 71a) (0.24 mmol) dissolved in dry DMF (2 mL) was added at 0° C. powdered NaOH (0.36 mmol, 14.5 mg, 1.5 eq) and the mixture was stirred for 1 hr at 0° C. Then chloro-methoxy-methane (19.3 μl, 1 eq) was added and the reaction stirred at 0° C. for 1 hour. The reaction was quenched with water (30 mL) and the mixture was extracted with dichloromethane. The organic phase was dried over MgSO4 and evaporated. The crude product was purified by preparative TLC (20% ethyl acetate/hexanes) to give 37.7 mg of (R)—N-(1-(methoxymethoxy)-4-methylpentan-2-yl)-3,4-dimethylbenzamide (53%). 1H NMR (500 MHz, CDCl3): δ 0.98-1.00 (t, 6H), 1.49-1.53 (m, 1H), 1.58-1.64 (m, 1H), 1.69-1.73 (m, 2H), 2.32-2.33 (d, 6H), 3.38-3.39 (t, 3H), 3.64-3.72 (ddd, 2H), 4.41-4.44 (m, 1H), 4.65-4.69 (dd, 2H), 6.37-6.39 (d, 1H), 7.19-7.21 (d, 1H), 7.50-7.52 (dd, 1H), 7.60 (sb, 1H). MS (M+H, 294.3).

後処理

  1. stirringthe reaction stirred at 0° C. for 1 hour
  2. customThe reaction was quenched with water (30 mL)
  3. extractionthe mixture was extracted with dichloromethane
  4. dry with materialThe organic phase was dried over MgSO4
  5. customevaporated
  6. customThe crude product was purified by preparative TLC (20% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-f63d130e191247cb821713b16b4cff8d
出典データセット
uspto-grants-2012_02
特許番号
US08124121B2

反応ノート

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