Methyl thiocyanate → 7-Hydroxy-2,2-dimethyl-chroman-6-carbonitrile

HRID 131162

반응식

HRID 131162 반응식
[CH3:1][C:2]1([CH3:13])[CH2:11][CH2:10][C:9]2[C:4](=[CH:5][C:6]([OH:12])=[CH:7][CH:8]=2)[O:3]1.B(Cl)(Cl)Cl.CS[C:20]#[N:21].[Cl-].[Cl-].[Cl-].[Al+3].[OH-].[Na+]>ClC(Cl)C.O>[OH:12][C:6]1[CH:5]=[C:4]2[C:9]([CH2:10][CH2:11][C:2]([CH3:13])([CH3:1])[O:3]2)=[CH:8][C:7]=1[C:20]#[N:21]

참가 물질

8

반응물 5

HCID 11168Methyl thiocyanateHCID 14798Sodium HydroxideHCID 25135Boron TrichlorideHCID 6451240Aluminum(III) ChlorideHCID 110412812,2-dimethyl-3,4-dihydro-2H-1-benzopyran-7-ol

생성물 1

HCID 218649767-Hydroxy-2,2-dimethyl-chroman-6-carbonitrile

시약·촉매·용매 2

HCID 962Water용매HCID 63651,1-Dichloroethane용매

실험 절차

In a 250 mL round-bottom flask was placed 2,2-dimethyl-Chroman-7-ol (1.76 g, 9.87 mmol, from Step 4-1-2) in 30 mL of dry dichloroethane under argon. The solution was cooled to 0° C. where boron trichloride (10.8 mL, 1M in CH2Cl2, 10.8 mmol, 1.1 eq) was added dropwise. At this point, methyl thiocyanate (0.80 g, 10.8 mmol, 1.1 eq) was added followed by aluminum trichloride (1.32 g, 9.87 mmol, 1 eq). The reaction was allowed to warm up to rt and stirred for 17 h. The reaction mixture was cooled down to 0° C. and 10 mL of 50% w/w NaOH was added to adjust the solution to PH˜14, followed by 40 mL of water. The solution was then refluxed at 65° C. for 2 h. The solution was allowed to cool to ambient temperature. The aqueous layer was washed with dichloromethane (20 mL). The aqueous solution was transferred to an Erlenmeyer flask and acidified to pH˜1 with conc. HCl. This solution was then extracted with EtOAc (3×20 mL) and the combined organic layers were dried over Na2SO4, filtered and evaporated. The residue was purified on silica gel (flash column chromatography) eluting with 5% ethyl acetate-hexane followed by 20% ethyl acetate-hexane to provide the desired product as white solid. The desired product was white solid (0.33 g, 16.5% ). 1H-NMR (CD3CN) δ 7.93 (broad s, 1H, OH), 7.26 (s, 1H), 6.28 (s, 1H), 2.69 (t, 2H), 1.80 (t, 2H), 1.32 (s, 6H).

후처리

  1. customIn a 250 mL round-bottom flask was placed
  2. additionwas added dropwise
  3. temperatureThe reaction mixture was cooled down to 0° C.
  4. temperatureThe solution was then refluxed at 65° C. for 2 h
  5. temperatureto cool to ambient temperature
  6. washThe aqueous layer was washed with dichloromethane (20 mL)
  7. extractionThis solution was then extracted with EtOAc (3×20 mL)
  8. dry with materialthe combined organic layers were dried over Na2SO4
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified on silica gel (flash column chromatography)
  12. washeluting with 5% ethyl acetate-hexane

출처 및 근거

ORD 기록
ord-c2b90f4bef874b4c92fa77c27e2fc91a
출처 데이터셋
uspto-grants-2008_06
특허 번호
US07384947B2

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