Potassium Carbonate → 4-Methylene-6-chloro-8-difluoromethoxychromane

HRID 1294481ノート

反応式

HRID 1294481 の反応式
CP(=O)(OC)OC.[CH2:8]([Li])[CH2:9][CH2:10][CH3:11].[Cl:13][C:14]1[CH:15]=[C:16]2[C:21](=[C:22]([O:24][CH:25]([F:27])[F:26])[CH:23]=1)[O:20]CCC2=O.[NH4+].[Cl-].C(=O)([O-])[O-].[K+].[K+]>C1COCC1.CCCCCC.O>[CH2:11]=[C:10]1[C:16]2[C:21](=[C:22]([O:24][CH:25]([F:27])[F:26])[CH:23]=[C:14]([Cl:13])[CH:15]=2)[O:20][CH2:8][CH2:9]1

参加物

9

反応物 5

HCID 11430Potassium CarbonateHCID 12958Dimethyl methylphosphonateHCID 25517Ammonium ChlorideHCID 227083496-Chloro-8-difluoromethoxychroman-4-oneHCID 178418339Butyllithium

生成物 1

HCID 227083434-Methylene-6-chloro-8-difluoromethoxychromane収率 47%

試薬・触媒・溶媒 3

HCID 962Water溶媒3 回HCID 8028Tetrahydrofuran溶媒2 回HCID 8058Hexane溶媒

反応条件

温度
120 °C

実験手順

To a solution of dimethyl methylphosphonate (8.9 g, 71.1 mmol) in dry THF (55 mL) under N2 was added, dropwise over 1 h at −70° C., n-butyllithium in hexane (1.6M, 49.2 mL). The mixture was stirred for 30 minutes at −70° C., whereafter a solution of 6-chloro-8-difluoromethoxychroman-4-one (6.8 g, 27.35 mmol, from step (v) above) in dry THF (15 mL) was added, dropwise over 30 minutes at −70° C. The reaction mixture was stirred for 2 h at −70° C., whereafter NH4Cl (aq., sat., 110 mL) was added, and then water (50 mL). The layers were separated and the aqueous phase was extracted with EtOAc. The combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was dissolved in DMF (85 mL). To the solution was added anhydrous potassium carbonate (27.4 g, 201.0 mmol) and water (3.6 ml). The mixture was warmed for 2 h at 120° C. (oil-bath). After the mixture had reached room temperature water (80 mL) was added. The mixture was extracted with EtOAc. The combined organic layers were washed with citric acid (aq., 10%) and with brine, dried (Na2SO4) and evaporated. The crude product was chromatographed on silica gel, eluting with heptane:methylene chloride (8:2), to afford 3.2 g (47%) of the sub-title compound.

後処理

  1. additionwas added, dropwise over 30 minutes at −70° C
  2. additionwas added
  3. customThe layers were separated
  4. extractionthe aqueous phase was extracted with EtOAc
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in DMF (85 mL)
  9. customhad reached room temperature
  10. additionwas added
  11. extractionThe mixture was extracted with EtOAc
  12. washThe combined organic layers were washed with citric acid (aq., 10%) and with brine
  13. dry with materialdried (Na2SO4)
  14. customevaporated
  15. customThe crude product was chromatographed on silica gel
  16. washeluting with heptane:methylene chloride (8:2)

出典と根拠

ORDレコード
ord-c698883e34864c18ad65159491d6f851
出典データセット
uspto-grants-2007_07
特許番号
US07241757B2

反応ノート

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