4-Methylmorpholine → Diethyl-N-[4-[[N-(tert-butyloxycarbonyl)amino]methyl]benzoyl]-L-glutamate

HRID 343823

反応式

HRID 343823 の反応式
[C:1]([O:5][C:6]([NH:8][CH2:9][C:10]1[CH:18]=[CH:17][C:13]([C:14]([OH:16])=O)=[CH:12][CH:11]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[CH2:35]([O:37][C:38](=[O:48])[C@H:39]([CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[NH2:40])[CH3:36]>CN(C=O)C>[CH2:35]([O:37][C:38](=[O:48])[C@H:39]([CH2:41][CH2:42][C:43]([O:45][CH2:46][CH3:47])=[O:44])[NH:40][C:14](=[O:16])[C:13]1[CH:12]=[CH:11][C:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[CH:18][CH:17]=1)[CH3:36]

参加物

6

反応物 4

HCID 79724-Methylmorpholine2 回HCID 62365Isobutyl chloroformateHCID 73960Glutamic acid diethyl ester hydrochlorideHCID 8536054-(((tert-Butoxycarbonyl)amino)methyl)benzoic acid

生成物 1

HCID 15292991Diethyl-N-[4-[[N-(tert-butyloxycarbonyl)amino]methyl]benzoyl]-L-glutamate収率 59%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

実験手順

A solution containing about 1.26 g of Compound 39 in about 20 ml anhydrous DMF under nitrogen was cooled in an ice-salt bath. About 0.55 ml of N-methylmorpholin was added to the cooled solution, followed 5 minutes later by about 0.65 ml isobutylchloroformate. After stirring for a period of about 20 minutes, 1.20 g diethyl-L-glutamate hydrochloride was added, followed immediately by about 0.55 ml N-methylmorpholin. The reaction mixture was warmed to room temperature and stirred for 12 hours. At this time, the activation cycle was repeated using 1/2 the amounts of reagents indicated above, after which the reaction mixture was warmed to room temperature and stirred for an additional 12 hours. The solvents were removed under reduced pressure, and the residue was dissolved in about 100 ml CH2Cl2, washed with about 75 ml water, 50 ml 0.1 NHCl, and about 50 ml saturated NaCl. The organic layers were dried (MgSO4) and filtered. The filtrate was evaporated under reduced pressure and the residue was flash chromatographed on silica gel (2.4×24 cm), eluting first with CH2Cl2 and then with 1% methanol in CH2Cl2. Fractions showing a single spot corresponding to the product were pooled and evaporated under reduced pressure to yield about 1.29 g of Compound 34.

後処理

  1. temperaturewas cooled in an ice-salt bath
  2. stirringstirred for 12 hours
  3. temperaturewas warmed to room temperature
  4. stirringstirred for an additional 12 hours
  5. customThe solvents were removed under reduced pressure
  6. dissolutionthe residue was dissolved in about 100 ml CH2Cl2
  7. washwashed with about 75 ml water, 50 ml 0.1 NHCl, and about 50 ml saturated NaCl
  8. dry with materialThe organic layers were dried (MgSO4)
  9. filtrationfiltered
  10. customThe filtrate was evaporated under reduced pressure
  11. customchromatographed on silica gel (2.4×24 cm)
  12. washeluting first with CH2Cl2
  13. customevaporated under reduced pressure

出典と根拠

ORDレコード
ord-50142f55e8184730832f3b0f2836cd56
出典データセット
uspto-grants-1999_01
特許番号
US05863920

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