Sodium Carbonate → (S)-methyl 2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate

HRID 472834ノート

反応式

HRID 472834 の反応式
[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:18])[C:3]=1[C:19](=[O:24])[C:20]([O:22][CH3:23])=[O:21].CB1N2CCC[C@@H]2C(C2C=CC=CC=2)(C2C=CC=CC=2)O1.C1(C)C=CC=CC=1.C(#N)C.C(=O)=O.C([O-])([O-])=O.[Na+].[Na+]>C1(C)C=CC=CC=1>[Cl:1][C:2]1[N:7]2[N:8]=[C:9]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([Cl:17])[CH:12]=3)[CH:10]=[C:6]2[N:5]=[C:4]([CH3:18])[C:3]=1[C@H:19]([OH:24])[C:20]([O:22][CH3:23])=[O:21]

参加物

6

反応物 4

HCID 10340Sodium CarbonateHCID 86587134Acetonitrile dry iceHCID 86670275Methyl 2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetateHCID 86670277(R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole toluene

生成物 1

HCID 86670276(S)-methyl 2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-hydroxyacetate収率 83%

試薬・触媒・溶媒 1

HCID 1140Toluene溶媒2 回

反応条件

温度
-40 °C

実験手順

To a stirred solution of methyl 2-(7-chloro-2-(3-chlorophenyl)-5-methylpyrazolo[1,5-a]pyrimidin-6-yl)-2-oxoacetate (1.8 g, 4.94 mmol) in anhydrous toluene (30 mL) was added 1.1M (R)-1-methyl-3,3-diphenylhexahydropyrrolo[1,2-c][1,3,2]oxazaborole/toluene (1.797 mL, 1.977 mmol). The mixture was cooled to −40° C. (acetonitrile/dry ice bath) and a solution of 50% (by weight) catechoborane in toluene (1.695 mL, 6.92 mmol) was added over 30 min. After stirred at −45-−35° C. for 2 hrs, the reaction mixture was stirred at −25° C.-−15° C. for additional 1 h. Saturated Na2CO3 solution (20 mL) was added to quench the reaction. The mixture was stirred vigorously for 30 min and extracted with EtOAc. The organic layer was washed with saturated Na2CO3 solution and dried (Na2SO4). The solvent was evaporated and the residue was purified by silica gel chromatography (15-50% EtOAc/hexane) to afford (1.5 g, 83%) of the title compound. 1H NMR (500 MHz, CHLOROFORM-d) δ 8.05-7.97 (m, 1H), 7.88 (dt, J=6.7, 1.8 Hz, 1H), 7.44-7.38 (m, 2H), 6.93 (s, 1H), 5.76 (s, 1H), 3.84 (s, 3H), 2.62 (s, 3H).

後処理

  1. stirringthe reaction mixture was stirred at −25° C.-−15° C. for additional 1 h
  2. customto quench
  3. customthe reaction
  4. stirringThe mixture was stirred vigorously for 30 min
  5. extractionextracted with EtOAc
  6. washThe organic layer was washed with saturated Na2CO3 solution
  7. dry with materialdried (Na2SO4)
  8. customThe solvent was evaporated
  9. customthe residue was purified by silica gel chromatography (15-50% EtOAc/hexane)

出典と根拠

ORDレコード
ord-929b40a3ef7349ba8de9bb166489a590
出典データセット
uspto-grants-2014_01
特許番号
US08633200B2

反応ノート

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