Ammonium Chloride → 6-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic acid 1'-tert-butyl ester 3'-methyl ester

HRID 2428181

反応式

HRID 2428181 の反応式
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH2:14][CH2:15][O:16][C:17]2[C:22]([Cl:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=2[Cl:25])=[N:11][CH:12]=1.[CH3:26][O:27][C:28]([C:30]1[CH2:31][N:32]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:33][CH2:34][C:35]=1OS(C(F)(F)F)(=O)=O)=[O:29].[NH4+].[Cl-]>C1COCC1.[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:26][O:27][C:28]([C:30]1[CH2:31][N:32]([C:44]([O:46][C:47]([CH3:50])([CH3:49])[CH3:48])=[O:45])[CH2:33][CH2:34][C:35]=1[C:7]1[CH:12]=[N:11][C:10]([O:13][CH2:14][CH2:15][O:16][C:17]2[C:22]([Cl:23])=[CH:21][C:20]([CH3:24])=[CH:19][C:18]=2[Cl:25])=[CH:9][CH:8]=1)=[O:29]

参加物

8

反応物 4

HCID 25517Ammonium ChlorideHCID 152219361-Tert-butyl 3-methyl 4-(trifluoromethanesulfonyloxy)-1,2,5,6-tetrahydropyridine-1,3-dicarboxylateHCID 448166685-Bromo-2-(2-(2,6-dichloro-4-methylphenoxy)ethoxy)pyridineHCID 178418339Butyllithium

生成物 1

HCID 671490666-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-5',6'-dihydro-2'H-[3,4']bipyridinyl-1',3'-dicarboxylic acid 1'-tert-butyl ester 3'-methyl ester収率 70.4%

試薬・触媒・溶媒 3

HCID 3007855Zincchloride触媒HCID 178418397HCID 178418397、化合物触媒HCID 8028Tetrahydrofuran溶媒2 回

実験手順

BuLi (1.6M in hexane, 39.3 mL, 45.2 mmol) was added to a sol. of 5-bromo-2-[2-(2,6-dichloro-4-methyl-phenoxy)-ethoxy]-pyridine (11.0 g, 28.3 mmol) in THF (700 mL) at −78° C. The mixture was stirred for 1 h, and ZnCl2 (0.71M in THF, 78.6 mL, 56.5 mmol) was added. This sol. was allowed to warm up to rt. A sol. of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 13.0 g, 34.5 mmol) in THF (30 mL) and Pd(PPh3)4 (814 mg, 0.704 mmol) were added. The mixture was stirred for 30 min at rt. Aq. sat. NH4Cl was added, and the mixture was extracted with EtOAc (2×). The combined org. extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC (EtOAc/heptane 1:9→1:1) yielded the title compound (10.7 g, 70%). LC-MS: tR=1.16 min; ES+: 537.33.

後処理

  1. stirringThe mixture was stirred for 30 min at rt
  2. extractionthe mixture was extracted with EtOAc (2×)
  3. dry with materialextracts were dried over MgSO4
  4. filtrationfiltered
  5. customthe solvents were removed under reduced pressure
  6. customPurification of the crude by FC (EtOAc/heptane 1:9→1:1)

出典と根拠

ORDレコード
ord-ac838eeca3a6474c9eb39643df27abd7
出典データセット
uspto-grants-2011_06
特許番号
US07968720B2

関連ノート

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