Sulfuric Acid → methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate

HRID 1912617ノート

反応式

HRID 1912617 の反応式
[F:1][C:2]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:17])=[C:12]([CH:15]=[O:16])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1.[Si](C#N)(C)(C)C.S(=O)(=O)(O)O.C[CH2:35][O:36][C:37](C)=[O:38]>ClCCl.[I-].[Zn+2].[I-]>[F:1][C:2]1[C:21]([F:22])=[CH:20][CH:19]=[CH:18][C:3]=1[CH2:4][N:5]1[C:9]2=[N:10][C:11]([CH3:17])=[C:12]([CH:15]([OH:16])[C:37]([O:36][CH3:35])=[O:38])[C:13]([I:14])=[C:8]2[CH:7]=[CH:6]1

参加物

7

反応物 4

HCID 1118Sulfuric AcidHCID 8857Ethyl AcetateHCID 82115Trimethylsilyl cyanideHCID 866757441-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde

生成物 1

HCID 71209168methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate収率 73.8%

試薬・触媒・溶媒 2

HCID 9883512zinc(II)iodide触媒HCID 6344Dichloromethane溶媒2 回

反応条件

温度
0 °C

実験手順

Steps I-J: To a solution of 1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridine-5-carbaldehyde (9.40 g, 19.84 mmol) in dichloromethane (DCM) (250 mL) at 0° C. was added TMSCN (10.64 mL, 79 mmol) followed by zinc iodide (12.67 g, 39.7 mmol) and the mixture was stirred at 0° C. for 5 min and then at ambient temperature for 1 h. The mixture was diluted with dichloromethane and washed with cold water, dried (Na2SO4), concentrated and dried in vacuo The residue was cooled to 0° C. and methanol (250 mL) was added followed by dropwise addition of sulfuric acid (50.8 mL, 952 mmol) and the mixture was stirred at 75° C. for 24 h. The mixture was diluted with EtOAc and washed with water. The aq. phase was extracted with EtOAc (2×) and the combined organic layers were washed with saturated NaHCO3/water, dried (Na2SO4), concentrated to provide methyl 2-(1-(2,3-difluorobenzyl)-4-iodo-6-methyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-2-hydroxyacetate (7.95 g, 14.65 mmol, 73.8% yield) as a yellow foam. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.62 (s, 3 H), 3.34-3.57 (m, 1 H), 3.78 (s, 3 H), 5.38-5.57 (m, 2 H), 5.88 (s, 1 H), 6.34 (d, J=3.52 Hz, 1 H), 6.81-6.90 (m, 1 H), 6.90-7.00 (m, 1 H), 7.01-7.13 (m, 1 H), 7.20 (d, J=3.52 Hz, 1 H); LCMS (m/z) ES+=473 (M+1).

後処理

  1. waitat ambient temperature for 1 h
  2. washwashed with cold water
  3. dry with materialdried (Na2SO4)
  4. concentrationconcentrated
  5. customdried in vacuo The residue
  6. temperaturewas cooled to 0° C.
  7. additionmethanol (250 mL) was added
  8. stirringthe mixture was stirred at 75° C. for 24 h
  9. washwashed with water
  10. extractionThe aq. phase was extracted with EtOAc (2×)
  11. washthe combined organic layers were washed with saturated NaHCO3/water
  12. dry with materialdried (Na2SO4)
  13. concentrationconcentrated

出典と根拠

ORDレコード
ord-d1f31c764f5247758cb470705cd2a8e8
出典データセット
uspto-grants-2013_12
特許番号
US08609653B2

反応ノート

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