Reaktion #953463

Reaktionsgleichung

potassium bicarbonate

diazomethane

Benzyl triphenyl phosphonium bromide

sodium hydride

N-Carbobenzyloxy-4-keto-L-proline

→

4-benzyl-L-proline methyl ester

Ausbeute 7.3%

Lösungsmittel

ether

water

DMSO

DMSO

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturheated at 70°-80° C.
2. 2
   workup.DISSOLUTIONuntil dissolved
3. 3
   TemperaturThe solution was cooled
4. 4
   TemperaturThe solution was heated at 70° for 4 hours
5. 5
   WaschenThe solution was washed with ether
6. 6
   ExtraktionThe product was extracted with chloroform
7. 7
   TrocknenThe chloroform solution was dried
8. 8
   Einengenconcentrated
9. 9
   SonstigeThe resulting oil was triturated with ether
10. 10
    ExtraktionThe ether solution was extracted with 10% sodium bicarbonate
11. 11
    ExtraktionThe acid was extracted with ether
12. 12
    SonstigeThe organic solution was dried
13. 13
    Einengenconcentrated
14. 14
    Sonstigewas esterified at 0° C.
15. 15
    Sonstigechromatographed over silica gel
16. 16
    Wascheneluted with ethyl acetate in hexane
17. 17
    SonstigeThe protecting group was removed
18. 18
    FiltrationThe solution was filtered through celite and
19. 19
    Einengenconcentrated

Vorschrift

Benzyl triphenyl phosphonium bromide (0.15 moles, 66.07 g) was added portionwise to a suspension of sodium hydride (0.15 moles, 6.0 g of 60% in mineral oil) in 350 ml DMSO and heated at 70°-80° 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 1 l of water was added. The solution was washed with ether and acidified to pH 4.0 using 2N 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 2N 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)

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