Potassium Carbonate → (3R)-N-[4'-(Hydroxymethyl)-3'-fluoro-1,1'-biphenyl-4-yl]-1-azabicyclo[2.2.2]octane-3-carboxamide
反応式
B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[K+].[K+].Br[C:26]1[CH:31]=[CH:30][C:29]([CH2:32][OH:33])=[C:28]([F:34])[CH:27]=1.Br[C:36]1[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]2[CH:50]3[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]3)[CH2:46]2)=[O:44])=[CH:38][CH:37]=1.[OH-].[Na+]>CN(C=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[OH:33][CH2:32][C:29]1[CH:30]=[CH:31][C:26]([C:36]2[CH:41]=[CH:40][C:39]([NH:42][C:43]([C@@H:45]3[CH:50]4[CH2:51][CH2:52][N:47]([CH2:48][CH2:49]4)[CH2:46]3)=[O:44])=[CH:38][CH:37]=2)=[CH:27][C:28]=1[F:34]参加物
8
反応物 5
生成物 1
試薬・触媒・溶媒 2
反応条件
- 温度
- 85 °C
実験手順
492 mg (1.62) of bis(pinacolato)diboron, 804 mg (5.82 mmol) of dry potassium carbonate, and 398 mg (1.94 mmol) of (4-bromo-2-fluorophenyl)methanol are dissolved in 4.2 ml of DMF. Argon is passed through the reaction mixture for 15 minutes, and then 59 mg (0.08 mmol) of PdCl2(dppf) are added, and the mixture is heated at 85° C. overnight. Then, 500 mg (1.62 mmol) of (3R)-N-(4-bromophenyl)-1-azabicyclo[2.2.2]octane-3-carboxamide, 8.1 ml of 1N sodium hydroxide solution and a further 59 mg (0.02 mmol) of PdCl2(dppf) are added. The mixture is heated at 85° C. overnight. The solvent is removed under reduced pressure. The crude product is purified by preparative HPLC. 21 mg (3% of theory) of the title compound are obtained.
後処理
- temperatureThe mixture is heated at 85° C. overnight
- customThe solvent is removed under reduced pressure
- customThe crude product is purified by preparative HPLC
出典と根拠
- ORDレコード
- ord-f2b2e38ec9ee40f9b1f25029cf5227c9
- 出典データセット
- uspto-grants-2006_11
- 特許番号
- US07138410B2
反応ノート
読み込み中…