Hydrochloric Acid → Methyl 5-[2-(benzyloxy)phenyl]-6-cyclohexyl-3-formyl-4-(methoxymethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate

HRID 1008995

反応式

HRID 1008995 の反応式
Br[C:2]1[N:6]([CH2:7][O:8][CH3:9])[C:5]2[CH:10]=[C:11]([C:13]([O:15][CH3:16])=[O:14])[S:12][C:4]=2[C:3]=1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1.[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1B(O)O)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[C:40]([O-])([O-])=[O:41].[Na+].[Na+].[OH-].[K+].CN(CCN(C)C)C.C([Li])CCC.[NH4+].[Cl-].Cl>O1CCOCC1.CO.C1COCC1.C1COCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.CN(C=O)C>[CH2:23]([O:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[C:2]1[N:6]([CH2:7][O:8][CH3:9])[C:5]2[C:10]([CH:40]=[O:41])=[C:11]([C:13]([O:15][CH3:16])=[O:14])[S:12][C:4]=2[C:3]=1[CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1

参加物

14

反応物 8

HCID 313Hydrochloric AcidHCID 8037N,N,N',N'-TetramethylethylenediamineHCID 10340Sodium CarbonateHCID 14797Potassium HydroxideHCID 25517Ammonium ChlorideHCID 2773253(2-(Benzyloxy)phenyl)boronic acidHCID 67298629methyl 5-bromo-6-cyclohexyl-4-(methoxymethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylateHCID 178418339Butyllithium

生成物 1

HCID 86629785Methyl 5-[2-(benzyloxy)phenyl]-6-cyclohexyl-3-formyl-4-(methoxymethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate収率 28%

試薬・触媒・溶媒 5

HCID 178418476HCID 178418476、化合物触媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒HCID 312751,4-Dioxane溶媒HCID 21899815MeOH tetrahydrofuran溶媒

反応条件

温度
40 °C

実験手順

Methyl 5-bromo-6-cyclohexyl-4-(methoxymethyl)-4H-thieno[3,2-b]pyrrole-2-carboxylate, 2-benzyloxyphenyl boronic acid (1.8 eq.) and Pd(PPh3)2Cl2 (0.3 eq.) were dissolved in dioxane (0.09M). 2M Na2CO3-solution (8.5 eq.) was added and after degassing the mixture was heated for 5 h to 110° C. All volatiles were evaporated i. vac. and the residual material was subjected to chromatography (PE:EtOAc, 4:1). The product fractions were evaporated and the sticky solid obtained was dissolved in MeOH/THF (1:1, 0.15 M) and 1M KOH-solution (excess) was added. The mixture was left stirring for 3 days at 40° C. All volatiles were evaporated i. vac. and the residual material was dissolved in water. The solution was acidified with 1N aq. HCl. The resulting suspension was extracted DCM. The organic phase was washed with brine and dried over Na2SO4. All volatiles were evaporated and the remaining solid was dissolved in THF (0.2M). This solution was added slowly at −78° C. to a mixture of TMEDA (5 eq.) and 1.6M n-butyl lithium (5 eq.) in THF, followed by the addition of an excess of DMF. After stirring for 30 min at −78° C. an excess of sat. aq. NH4Cl-solution was added and the mixture was left standing for 90 min at −78° C. Then the mixture was transferred into an excess of 0.2N aq. HCl. The mixture was extracted with DCM, the organic phase was washed with brine, dried over Na2SO4 and all volatiles were evaporated i. vac. The residual material was dissolved in DMF (0.5M) and an excess of K2CO3 was added, followed by an excess of methyl iodide. The mixture was left stirring over night, then all volatiles were evaporated. The residual material was purified by chromatography (PE:EtOAc, 8.5:1.5) to give a yellow solid (28%). MS (ES+) m/z 518 (M+H)+.

後処理

  1. customafter degassing the mixture
  2. temperaturewas heated for 5 h to 110° C
  3. customAll volatiles were evaporated i
  4. customThe product fractions were evaporated
  5. customthe sticky solid obtained
  6. waitThe mixture was left
  7. customAll volatiles were evaporated i
  8. dissolutionand the residual material was dissolved in water
  9. extractionThe resulting suspension was extracted DCM
  10. washThe organic phase was washed with brine
  11. dry with materialdried over Na2SO4
  12. customAll volatiles were evaporated
  13. dissolutionthe remaining solid was dissolved in THF (0.2M)
  14. additionwas added
  15. waitthe mixture was left
  16. waitstanding for 90 min at −78° C
  17. extractionThe mixture was extracted with DCM
  18. washthe organic phase was washed with brine
  19. dry with materialdried over Na2SO4
  20. customall volatiles were evaporated i
  21. dissolutionThe residual material was dissolved in DMF (0.5M)
  22. additionan excess of K2CO3 was added
  23. waitThe mixture was left
  24. stirringstirring over night
  25. customall volatiles were evaporated
  26. customThe residual material was purified by chromatography (PE:EtOAc, 8.5:1.5)

出典と根拠

ORDレコード
ord-4c03cec4ffbf49a397a46f57bbee6939
出典データセット
uspto-grants-2011_07
特許番号
US07973026B2

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