Diazomethane → 4-benzyl-L-proline methyl ester

HRID 1938627

反応式

HRID 1938627 の反応式
[Br-].[CH2:2]([P+](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[H-].[Na+].C([N:40]1[CH2:47][C:46](=O)[CH2:45][C@H:41]1[C:42]([OH:44])=[O:43])(OCC1C=CC=CC=1)=O.[C:49](=O)(O)[O-].[K+].[N+](=C)=[N-]>CS(C)=O.O.CCOCC.CO.[Pd]>[CH3:49][O:44][C:42](=[O:43])[C@@H:41]1[CH2:45][CH:46]([CH2:2][C:3]2[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH2:47][NH:40]1

参加物

11

反応物 5

HCID 9550DiazomethaneHCID 24758Sodium hydrideHCID 516893Potassium BicarbonateHCID 2734970Benzyltriphenylphosphonium bromideHCID 11076282N-Carbobenzyloxy-4-keto-L-proline

生成物 1

HCID 545261924-benzyl-L-proline methyl ester収率 7.3%

試薬・触媒・溶媒 5

HCID 23938Palladium触媒HCID 679Dimethyl Sulfoxide溶媒2 回HCID 887Methanol溶媒HCID 962Water溶媒HCID 3283Diethyl Ether溶媒

反応条件

温度
80 °C

実験手順

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.

後処理

  1. dissolutionuntil dissolved
  2. temperatureThe solution was cooled
  3. temperatureThe solution was heated at 70° for 4 hours
  4. washThe solution was washed with ether
  5. extractionThe product was extracted with chloroform
  6. dry with materialThe chloroform solution was dried
  7. concentrationconcentrated
  8. customThe resulting oil was triturated with ether
  9. extractionThe ether solution was extracted with 10% sodium bicarbonate
  10. extractionThe acid was extracted with ether
  11. customThe organic solution was dried
  12. concentrationconcentrated
  13. customwas esterified at 0° C.
  14. customchromatographed over silica gel
  15. washeluted with ethyl acetate in hexane
  16. customThe protecting group was removed
  17. filtrationThe solution was filtered through celite and
  18. concentrationconcentrated

出典と根拠

ORDレコード
ord-c86c7c5ecf0645feb2e73604ffa58d0f
出典データセット
uspto-grants-1997_12
特許番号
US05693633

関連ノート

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