反応 #1052797

反応方程式

N-t-butoxycarbonyl-D-serine

sodium hydride

1,3-dichloro-5-chloromethyl-benzene

HCl

→

title compound

2-tert-Butoxycarbonylamino-3-(3,5-dichloro-benzyloxy)-Propionic acid

溶媒

N,N-dimethylformamide

ethyl ether

反応条件

後処理

1. 1
   その他The reaction was then quenched with 1N NaOH
2. 2
   抽出the mixture extracted three times with dichloromethane
3. 3
   洗浄The combined organic layers were then washed three times with water, 1N HCl
4. 4
   乾燥dried over anhydrous magnesium sulfate
5. 5
   ろ過filtered
6. 6
   濃縮concentrated in vacuo
7. 7
   その他to give crude product
8. 8
   抽出the mixture was extracted three times with dichloromethane
9. 9
   洗浄washed three times each with water and brine
10. 10
    乾燥then dried over anhydrous magnesium sulfate
11. 11
    ろ過filtered
12. 12
    濃縮concentrated in vacuo
13. 13
    その他to give an additional 620 mg of crude product
14. 14
    その他purified by silica gel chromatography

実験手順

To a stirred solution of N-t-butoxycarbonyl-D-serine (10.0 g, 48.7 mol) in N,N-dimethylformamide (150 mL) at about 0° C. was added sodium hydride (4.0 g, 60% dispersion in mineral oil, 99.84 mmol) portionwise. The mixture was stirred for about 30 minutes, and then a solution of 1,3-dichloro-5-chloromethyl-benzene (9.5 mL, 48.7 mmol) in ethyl ether (40 mL) was added. The reaction was allowed to slowly warm to room temperature overnight. The reaction was then quenched with 1N NaOH, the mixture extracted three times with dichloromethane. The combined organic layers were then washed three times with water, 1N HCl, dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give crude product. The original basic aqueous layer was then acidified to about pH 4 with 1N HCl, and the mixture was extracted three times with dichloromethane. These three organic layers were combined and washed three times each with water and brine then dried over anhydrous magnesium sulfate, filtered and concentrated in vacuo to give an additional 620 mg of crude product. Both product fractions were combined and purified by silica gel chromatography using 5% methanol/chloroform as eluent and yielded the title compound of part 1-E (12.39 g, 70%): −APcI MS (M−1)− 363, (M−3)− 361; 1H NMR=400 MHz (CDCl3) δ: 7.13 (arom, s, 3H), 5.42 (NH, d, 1H), 4.50 (CHCO2H, m, 1H), 4.45 (PhCH2O, s, 2H), 3.82 (CH2OBz, d of d, 2H), 1.43 (BOC, s, 9H).

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