Isobutyl chloroformate → tert-butyl (2S,4S)-2-[(5-bromo-2-carbamoylthiophen-3-yl)carbamoyl]-4-methylpyrrolidine-1-carboxylate

HRID 1426437ノート

反応式

HRID 1426437 の反応式
[C:1]([O:5][C:6]([N:8]1[CH2:15][C@@H:14]([CH3:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)OCC(C)C.[NH2:25][C:26]1[CH:30]=[C:29]([Br:31])[S:28][C:27]=1[C:32]([NH2:34])=[O:33].C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.C(N(CC)CC)C>[Br:31][C:29]1[S:28][C:27]([C:32](=[O:33])[NH2:34])=[C:26]([NH:25][C:10]([C@@H:9]2[CH2:13][C@H:14]([CH3:16])[CH2:15][N:8]2[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:12])[CH:30]=1

参加物

8

反応物 4

HCID 62365Isobutyl chloroformateHCID 516892Sodium BicarbonateHCID 219758623-Amino-5-bromothiophene-2-carboxamideHCID 26596883(4S)-1-(tert-Butoxycarbonyl)-4-methyl-L-proline

生成物 1

HCID 86676210tert-butyl (2S,4S)-2-[(5-bromo-2-carbamoylthiophen-3-yl)carbamoyl]-4-methylpyrrolidine-1-carboxylate収率 68.6%

試薬・触媒・溶媒 3

HCID 8028Tetrahydrofuran溶媒HCID 8471Triethylamine溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (4S)-1-(tert-butoxycarbonyl)-4-methyl-L-proline (491 mg) and triethylamine (0.353 mL) in tetrahydrofuran (5 mL) was added 2-methylpropyl chlorocarbonate (0.292 mL) at 0° C., and the mixture was stirred at room temperature for 1 hr. Thereafter, to the reaction system was added 3-amino-5-bromothiophene-2-carboxamide (225 mg) produced in Example 1, step D, and the mixture was stirred at 60° C. for 24 hr. Ethyl acetate (20 mL) and aqueous sodium hydrogen carbonate (10 mL) were added to the reaction mixture, and the separated aqueous layer was extracted with ethyl acetate (5 mL). The combined organic layers were washed with brine (5 mL) and dried over anhydrous sodium sulfate. Insoluble material was filtered off, the filtrate was concentrated under reduced pressure, and the residue was crystallized from ethanol (5 mL). The obtained colorless solid was fractionated by high performance liquid chromatography (column: CHIRALPAK AD (50 mm i.d.×500 mm L, manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.), mobile phase: hexane/ethanol (850/150), flow rate: 80 mL/min, column temperature: 30° C.) to give the title compound (302 mg) as a colorless solid.

後処理

  1. stirringthe mixture was stirred at 60° C. for 24 hr
  2. extractionthe separated aqueous layer was extracted with ethyl acetate (5 mL)
  3. washThe combined organic layers were washed with brine (5 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationInsoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customthe residue was crystallized from ethanol (5 mL)
  8. customwas fractionated by high performance liquid chromatography (column: CHIRALPAK AD (50 mm i.d.×500 mm L, manufactured by DAICEL CHEMICAL INDUSTRIES, LTD.), mobile phase: hexane/ethanol (850/150), flow rate: 80 mL/min, column temperature: 30° C.)

出典と根拠

ORDレコード
ord-850e5550b2874962bdda743f756a6fb1
出典データセット
uspto-grants-2015_01
特許番号
US08933069B2

反応ノート

読み込み中…