反応 #1063789

反応方程式

potassium bicarbonate

diazomethane

Benzyl triphenyl phosphonium bromide

sodium

N-Carbobenzyloxy-4-keto-L-proline

→

4-benzyl-L-proline methyl ester

収率 7.3%

溶媒

water

ether

methanol

DMSO

DMSO

反応条件

後処理

1. 1
   温度heated at 70°-80.COPYRGT.C
2. 2
   workup.DISSOLUTIONuntil dissolved
3. 3
   温度The solution was cooled
4. 4
   温度The solution was heated at 70° for 4 hours
5. 5
   洗浄The solution was washed with ether
6. 6
   抽出The product was extracted with chloroform
7. 7
   乾燥The chloroform solution was dried
8. 8
   濃縮concentrated
9. 9
   その他The resulting oil was triturated with ether
10. 10
    抽出The ether solution was extracted with 10% sodium bicarbonate
11. 11
    抽出The acid was extracted with ether
12. 12
    その他The organic solution was dried
13. 13
    濃縮concentrated
14. 14
    その他was esterified at 0° C.
15. 15
    その他chromatographed over silica gel
16. 16
    洗浄eluted with ethyl acetate in hexane
17. 17
    その他The protecting group was removed
18. 18
    ろ過The solution was filtered through celite and
19. 19
    濃縮concentrated

実験手順

Benzyl triphenyl phosphonium bromide (0.15 moles, 66.07 g) was added portionwise to a suspension of sodium (0.15 moles, 6.0 g of 60% in mineral oil) in 350 ml DMSO and heated at 70°-80.COPYRGT.C until dissolved. The solution was cooled. N-Carbobenzyloxy-4-keto-L-proline (0.025 moles, 13.2 g) in 50 ml DMSO was added dropwise. The solution was heated at 70° for 4 hours and stirred at room temperature overnight. A solution of 15 g potassium bicarbonate in 11 of water was added. The solution was washed with ether and acidified to pH 4.0 using 2 N HCl. The product was extracted with chloroform. The chloroform solution was dried and concentrated. The resulting oil was triturated with ether. The ether solution was extracted with 10% sodium bicarbonate. The aqueous layer was acidified with 2 N HCl. The acid was extracted with ether. The organic solution was dried and concentrated. (MS) The acid (5.9 mmoles, 2.0 g) in ether was esterified at 0° C. with an excess of diazomethane and chromatographed over silica gel eluted with ethyl acetate in hexane. The protecting group was removed by dissolving the ester (2.7 mmoles, 0.9 g) in 20 ml methanol and hydrogenating over Pd/C (200 mg) for 4 hours at 30 psi. The solution was filtered through celite and concentrated to yield 400 mg of 4-benzyl-L-proline methyl ester. (MS)

出典