Phthalide → o-(Hydroxymethyl)benzamide

HRID 2054127

反応式

HRID 2054127 の反応式
C([N:3](CC)CC)C.[Al+3].[Cl-].[Cl-].[Cl-].[C:12]1([C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[CH2:15][O:14]1)=[O:13].CCOC(C)=O>ClCCCl>[OH:14][CH2:15][C:16]1[CH:17]=[CH:18][CH:19]=[CH:20][C:21]=1[C:12]([NH2:3])=[O:13]

参加物

6

反応物 4

HCID 6885PhthalideHCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 6451240Aluminum(III) Chloride

生成物 1

HCID 99176o-(Hydroxymethyl)benzamide収率 97.5%

試薬・触媒・溶媒 1

HCID 111,2-Dichloroethane溶媒3 回

反応条件

温度
17.5 °C

実験手順

A solution of triethylamine (TEA, 0.824 g, 1.13 ml, 8.14 mmol, 1.5 equiv.) in 1,2-dichloroethane (3 ml) was added dropwise under stirring and cooling with ice to a suspension of AlCl3 (0.796 g, 5.97 mmol, 1.1 equiv.) in 1,2-dichloroethane (7 ml). The temperature was maintained at 15-20° C. during the addition and the mixture was then allowed to warm up at room temperature. A solution of 1-dimethoxytrityl-6-amino-hexan-1-ol (16) (2.505 g, 5.97 mmol, 1.1 equiv., prepared as described by Woo and Fung (1996), International Pat. App. Pub. No. WO 96/05215, which is incorporated herein by reference in its entirety) and phthalide (17) (0.728 g, 5.43 mmol, 1.0 equiv.) in 1,2-dichloroethane (3 ml) was added over a period of 20 min and the mixture was stirred at room temperature overnight. The completion of the reaction was confirmed by TLC analysis (EtOAc containing 1% TEA). The reaction mixture was then quenched with an ice-water mixture (30 ml) and stirred for further 30 min. The resulting suspension was filtered through a bed of Celite® and the filter cake was washed with 1,2-dichloroethane (10 ml). The organic phase of the combined filtrates was separated, washed with water (30 ml) and brine (20 ml), dried over MgSO4 and concentrated. The crude product was purified by flash chromatography (15-70% EtOAc in hexanes containing 1% of TEA, gradient elution) yielding 0.80 g (27%) of compound (19) as a pale yellow oil. Rf=0.68 (EtOAc containing 1% TEA). 1H NMR (400 MHz, CD3CN) δ 7.61-7.19 (m, 14H), 6.85 (d, J=8.9 Hz, 4H), 5.33 (s, 1H), 4.50 (s, 2H), 3.75 (s, 6H), 3.32 (q, J=6.6 Hz, 2H), 3.01 (t, J=6.6 Hz, 2H), 1.63-1.53 (m, 4H), 1.44-1.28 (m, 4H).

後処理

  1. temperatureto warm up at room temperature
  2. additionwas added over a period of 20 min
  3. stirringthe mixture was stirred at room temperature overnight
  4. customThe reaction mixture was then quenched with an ice-water mixture (30 ml)
  5. stirringstirred for further 30 min
  6. filtrationThe resulting suspension was filtered through a bed of Celite®
  7. washthe filter cake was washed with 1,2-dichloroethane (10 ml)
  8. customThe organic phase of the combined filtrates was separated
  9. washwashed with water (30 ml) and brine (20 ml)
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated
  12. customThe crude product was purified by flash chromatography (15-70% EtOAc in hexanes containing 1% of TEA, gradient elution)

出典と根拠

ORDレコード
ord-d25e10a969004959a8ca2d87a0b7144b
出典データセット
uspto-grants-2008_02
特許番号
US07329515B2

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