Sodium Carbonate → (rac.)-(1R*,5S*)-7-{6-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-pyridin-3-yl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester

HRID 2428186ノート

反応式

HRID 2428186 の反応式
[CH2:1]([O:3][C:4]([C:6]1[C@@H:7]2[N:22]([CH3:23])[C@H:11]([CH2:12][C:13]=1OS(C(F)(F)F)(=O)=O)[CH2:10][N:9]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:8]2)=[O:5])[CH3:2].[Cl:31][C:32]1[C:37]([F:38])=[CH:36][CH:35]=[C:34]([F:39])[C:33]=1[C:40]1[CH:44]=[C:43]([CH2:45][O:46][C:47]2[CH:52]=[CH:51][C:50](B3OC(C)(C)C(C)(C)O3)=[CH:49][N:48]=2)[O:42][N:41]=1.C([O-])([O-])=O.[Na+].[Na+]>COCCOC.CCOC(C)=O.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>[CH2:1]([O:3][C:4]([C:6]1[C@@H:7]2[N:22]([CH3:23])[C@H:11]([CH2:12][C:13]=1[C:50]1[CH:49]=[N:48][C:47]([O:46][CH2:45][C:43]3[O:42][N:41]=[C:40]([C:33]4[C:34]([F:39])=[CH:35][CH:36]=[C:37]([F:38])[C:32]=4[Cl:31])[CH:44]=3)=[CH:52][CH:51]=1)[CH2:10][N:9]([C:24]([O:26][C:27]([CH3:30])([CH3:29])[CH3:28])=[O:25])[CH2:8]2)=[O:5])[CH3:2]

参加物

7

反応物 3

HCID 10340Sodium CarbonateHCID 44158352(rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl esterHCID 671487962-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine

生成物 1

HCID 131728976(rac.)-(1R*,5S*)-7-{6-[3-(2-Chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-pyridin-3-yl}-9-methyl-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic Acid 3-tert-butyl Ester 6-ethyl Ester収率 81.4%

試薬・触媒・溶媒 3

HCID 178418397HCID 178418397、化合物触媒HCID 80711,2-Dimethoxyethane溶媒HCID 8857Ethyl Acetate溶媒

反応条件

温度
80 °C

実験手順

(rac.)-(1R*,5S*)-9-Methyl-7-trifluoromethanesulfonyloxy-3,9-diaza-bicyclo[3.3.1]non-6-ene-3,6-dicarboxylic acid 3-tert-butyl ester 6-ethyl ester (WO 2003/093267; 1.00 g, 2.18 mmol) and 2-[3-(2-chloro-3,6-difluoro-phenyl)-isoxazol-5-ylmethoxy]-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-pyridine (1.41 g, 3.27 mmol) were dissolved in DME (14.5 mL), and aq. 2M Na2CO3 (11.0 mL) was added. The mixture was degassed with N2 (5 min). Pd(PPh3)4 (126 mg, 0.109 mmol) was added, and the mixture was rapidly heated to 80° C. The mixture was stirred at this temperature for 1 h, and was allowed to cool to rt. The mixture was diluted with EtOAc (100 mL), and was washed with water (100 mL). The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the crude by FC(CH2Cl2/MeOH 95:5) yielded the title compound (1.12 g, 81%). LC-MS: tR=0.91 min; ES+: 631.34.

後処理

  1. customThe mixture was degassed with N2 (5 min)
  2. temperatureto cool to rt
  3. washwas washed with water (100 mL)
  4. dry with materiallayer was dried over MgSO4
  5. filtrationfiltered
  6. customthe solvents were removed under reduced pressure
  7. customPurification of the crude by FC(CH2Cl2/MeOH 95:5)

出典と根拠

ORDレコード
ord-8fcea0fde9c547858f3300d88722485c
出典データセット
uspto-grants-2011_06
特許番号
US07968720B2

反応ノート

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