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

반응식

HRID 2428181 반응식
[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]

참가 물질

8

반응물 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

생성물 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 ester수율 70.4%

시약·촉매·용매 3

HCID 3007855Zincchloride촉매HCID 178418397HCID 178418397, 화합물촉매HCID 8028Tetrahydrofuran용매2회

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-ac838eeca3a6474c9eb39643df27abd7
출처 데이터셋
uspto-grants-2011_06
특허 번호
US07968720B2

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