Tetrabutylammonium Fluoride → 4-[1,3]Dioxolan-2-yl-2-fluorophenol

HRID 492591노트

반응식

HRID 492591 반응식
[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:22]=[CH:21][C:9]([O:10][Si](C(C)C)(C(C)C)C(C)C)=[C:8]([F:23])[CH:7]=1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC.CCCCCCC.C(OCC)(=O)C>C1COCC1.ClCCl>[O:1]1[CH2:5][CH2:4][O:3][CH:2]1[C:6]1[CH:22]=[CH:21][C:9]([OH:10])=[C:8]([F:23])[CH:7]=1

참가 물질

6

반응물 3

HCID 2724141Tetrabutylammonium FluorideHCID 21899848Ethylacetate heptaneHCID 59730094(4-[1,3]Dioxolan-2-yl-2-fluorophenoxy)triisopropylsilane

생성물 1

HCID 184436734-[1,3]Dioxolan-2-yl-2-fluorophenol수율 52%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 8028Tetrahydrofuran용매2회

실험 절차

To a solution of (4-[1,3]dioxolan-2-yl-2-fluorophenoxy)triisopropylsilane (Example 93. Part B) (105.9 g, approximately 0.311 mol) in THF (1.589 L) add 1.0 M tetrabutylammonium fluoride (TBAF) in THF (311 mL) in a steady stream over 5 min at 23-27° C. without cooling. Stir for 1 hr till the reaction complete by TLC (19:1 heptane/ethyl acetate). Concentrate to a red oil and partition between ether (500 mL) and deionized water (1 L). Separate the layers and extract the aqueous layer with ether (500 mL). Combine the ether layers, wash with brine and dry over sodium sulfate. Filter and concentrate to give the crude product (92.9 g. Dissolve the crude product in dichloromethane and filter through 400 g of silica gel 60. Wash with dichloromethane (3× 1 L fractions) and concentrate the combined filtrate to give an impure product. Crystallize from dichloromethane/heptane to give the title compound (29.8 g, 52%). Gas chromatography: retention time 15.96 min (30 m×0.32 mm i.d. DB-1 column, 0.25 micron film thickness; 1.2 mL/min flow rate; 55:1 split ratio; temperature profile: 35° C./3 min, 10° C. temperature increase per min; 250° C./10.5 min). 1H NMR (DMSO-d6) δ 3.84-3.93 (m, 2H, CH2), 3.93-4.04 (m, 2H, CH2), 5.60 (s, 1H, CH), 6.91 (t, 11, ArH), 7.06 (dd, 1H, ArH), 7.15 (dd, 1H, ArH), 10.0 (s, 1H, OH).

후처리

  1. temperaturewithout cooling
  2. concentrationConcentrate to a red oil
  3. custompartition between ether (500 mL) and deionized water (1 L)
  4. customSeparate the layers
  5. extractionextract the aqueous layer with ether (500 mL)
  6. washCombine the ether layers, wash with brine
  7. dry with materialdry over sodium sulfate
  8. filtrationFilter
  9. concentrationconcentrate
  10. customto give the crude product (92.9 g
  11. filtrationfilter through 400 g of silica gel 60
  12. washWash with dichloromethane (3× 1 L fractions)
  13. concentrationconcentrate the combined filtrate
  14. customto give an impure product
  15. customCrystallize from dichloromethane/heptane

출처 및 근거

ORD 기록
ord-ea4e798a2d4843c585a210f1af2a3889
출처 데이터셋
uspto-grants-2009_05
특허 번호
US07531557B2

반응 노트

불러오는 중…