Binap, (A+-)- → 4-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl]-piperazine-1-carboxylic acid benzyl ester

HRID 79738

反応式

HRID 79738 の反応式
[CH3:1][O:2][C:3](=[O:36])[NH:4][CH:5]([C:9]([N:11]1[CH2:15][CH2:14][CH2:13][CH:12]1[C:16]1[N:17]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:18]([C:21]2[CH:26]=[CH:25][C:24](Br)=[CH:23][CH:22]=2)=[CH:19][N:20]=1)=[O:10])[CH:6]([CH3:8])[CH3:7].[C:37]([N:47]1[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]1)([O:39][CH2:40][C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1)=[O:38].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+]>C1(C)C=CC=CC=1.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH2:40]([O:39][C:37]([N:47]1[CH2:52][CH2:51][N:50]([C:24]2[CH:25]=[CH:26][C:21]([C:18]3[N:17]([CH2:28][O:29][CH2:30][CH2:31][Si:32]([CH3:35])([CH3:34])[CH3:33])[C:16]([CH:12]4[CH2:13][CH2:14][CH2:15][N:11]4[C:9](=[O:10])[CH:5]([NH:4][C:3]([O:2][CH3:1])=[O:36])[CH:6]([CH3:8])[CH3:7])=[N:20][CH:19]=3)=[CH:22][CH:23]=2)[CH2:49][CH2:48]1)=[O:38])[C:41]1[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=1

参加物

7

反応物 4

HCID 634876Binap, (A+-)-HCID 643495Benzyl piperazine-1-carboxylateHCID 23676156Sodium t-butoxideHCID 66620156(1-{2-[5-(4-bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl)-2-methyl-propyl)-carbamic acid methyl ester

生成物 1

HCID 666202604-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl]-piperazine-1-carboxylic acid benzyl ester収率 13%

試薬・触媒・溶媒 2

HCID 167845palladium(II) acetate触媒HCID 1140Toluene溶媒

反応条件

温度
110 °C

実験手順

(1-{2-[5-(4-Bromo-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (1033 mg, 1.8 mmol) and 4-Cbz-piperazine (588 mg, 2.7 mmol) in toluene (9 mL) were treated with Pd(OAc)2 (20 mg, 0.09 mmol), BINAP (110 mg, 0.1 mmol), and NaOtBu (428 mg, 4.45 mmol). The mixture was stirred in a sealed tube at 110° C. for 18 hours. The solution was concentrated, diluted with EtOAc (50 mL), and washed with saturated NaHCO3 (20 mL), H2O (20 mL), and brine (20 mL). The solution was dried over MgSO4 and subjected to a 120 g SiO2 COMBIFLASH column (0-100% EtOAc-hexanes gradient) to afford 4-{4-[2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-3-(2-trimethylsilanyl-ethoxymethyl)-3H-imidazol-4-yl]-phenyl}-piperazine-1-carboxylic acid benzyl ester (166 mg, 13%): MS (ESI) m/z 719 [M+H]+.

後処理

  1. concentrationThe solution was concentrated
  2. additiondiluted with EtOAc (50 mL)
  3. washwashed with saturated NaHCO3 (20 mL), H2O (20 mL), and brine (20 mL)
  4. dry with materialThe solution was dried over MgSO4

出典と根拠

ORDレコード
ord-afe771c8ba234f709bce621c3c7e4a9c
出典データセット
uspto-grants-2014_09
特許番号
US08841278B2

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