1,2-Dichloroethane → Methyl N-{[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valyl-(4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate

HRID 1511548ノート

反応式

HRID 1511548 の反応式
Cl.[CH:2]([C:4]1[CH:12]=[CH:11][CH:10]=[C:9]2[C:5]=1[CH2:6][N:7]([C:13]([O:15][C@@H:16]1[CH2:20][C@@H:19]([C:21]([O:23][CH3:24])=[O:22])[NH:18][CH2:17]1)=[O:14])[CH2:8]2)=[CH2:3].[CH3:25][C:26]([CH3:44])([CH2:40][CH2:41][CH:42]=[CH2:43])[CH2:27][O:28][C:29]([NH:31][C@H:32]([C:37](O)=[O:38])[C:33]([CH3:36])([CH3:35])[CH3:34])=[O:30].CCN(C(C)C)C(C)C.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1>CN(C=O)C.CCOCC>[CH3:25][C:26]([CH3:44])([CH2:40][CH2:41][CH:42]=[CH2:43])[CH2:27][O:28][C:29]([NH:31][C@H:32]([C:37]([N:18]1[CH2:17][C@H:16]([O:15][C:13]([N:7]2[CH2:6][C:5]3[C:9](=[CH:10][CH:11]=[CH:12][C:4]=3[CH:2]=[CH2:3])[CH2:8]2)=[O:14])[CH2:20][C@H:19]1[C:21]([O:23][CH3:24])=[O:22])=[O:38])[C:33]([CH3:34])([CH3:35])[CH3:36])=[O:30]

参加物

8

反応物 5

HCID 111,2-DichloroethaneHCID 81531DiisopropylethylamineHCID 181649HOAtHCID 45379499(S)-2-((((2,2-Dimethylhex-5-en-1-yl)oxy)carbonyl)amino)-3,3-dimethylbutanoic acidHCID 45379932(3R,5S)-5-(Methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate Hydrochloride

生成物 1

HCID 45379615Methyl N-{[(2,2-dimethylhex-5-en-1-yl)oxy]carbonyl}-3-methyl-L-valyl-(4R)-4-{[(4-vinyl-1,3-dihydro-2H-isoindol-2-yl)carbonyl]oxy}-L-prolinate収率 50.7%

試薬・触媒・溶媒 2

HCID 3283Diethyl Ether溶媒HCID 6228Dimethylformamide溶媒

実験手順

To a solution of (3R,5S)-5-(methoxycarbonyl)pyrrolidin-3-yl 4-vinyl-1,3-dihydro-2H-isoindole-2-carboxylate hydrochloride (5.0 g, 14.2 mmol) and N-{[(2,2-dimethylhex-5-enyl)oxy]carbonyl}-3-methyl-L-valine (4.0 g, 14.2 mmol) in DMF (20 ml) at RT was added DIPEA (2.5 mL, 14.2 mmol), EDC (5.5 g, 28.4 mmol), and HOAt (1.9 g, 14.2 mmol). After 18 h the reaction mixture was poured into Et2O, and extracted with 1 N HCl. The aqueous layer was extracted with EtOAc, and the combined organic layers were washed with 1 N HCl, water, NaHCO3, and brine. The organic layer was dried over MgSO4 and the solvent was removed in vacuo. The crude product was purified on silica (30% EtOAc in hexanes) to yield 4.2 g of the title compound as a thick oil. LRMS (ESI) m/z 584.4 [(M+H)+; calcd for C32H46N3O7: 584.3].

後処理

  1. extractionextracted with 1 N HCl
  2. extractionThe aqueous layer was extracted with EtOAc
  3. washthe combined organic layers were washed with 1 N HCl, water, NaHCO3, and brine
  4. dry with materialThe organic layer was dried over MgSO4
  5. customthe solvent was removed in vacuo
  6. customThe crude product was purified on silica (30% EtOAc in hexanes)

出典と根拠

ORDレコード
ord-4211c4f4ebba4c2c97e606d9db86c54c
出典データセット
uspto-grants-2012_07
特許番号
US08216999B2

反応ノート

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