4-Methoxy-alpha-toluenethiol → Ethyl 2-fluoro-3-((4-methoxybenzyl)thio)benzoate

HRID 522748노트

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HRID 522748 반응식
Br[C:2]1[C:3]([F:13])=[C:4]([CH:10]=[CH:11][CH:12]=1)[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH3:14][O:15][C:16]1[CH:21]=[CH:20][C:19]([CH2:22][SH:23])=[CH:18][CH:17]=1.C(N(C(C)C)CC)(C)C>O1CCOCC1.CCCCCC.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2>[F:13][C:3]1[C:2]([S:23][CH2:22][C:19]2[CH:20]=[CH:21][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)=[CH:12][CH:11]=[CH:10][C:4]=1[C:5]([O:7][CH2:8][CH3:9])=[O:6]

참가 물질

8

반응물 3

HCID 804074-Methoxy-alpha-toluenethiolHCID 81531DiisopropylethylamineHCID 17832538Ethyl 3-bromo-2-fluorobenzoate

생성물 1

HCID 66764575Ethyl 2-fluoro-3-((4-methoxybenzyl)thio)benzoate수율 88%

시약·촉매·용매 4

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)촉매HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8058Hexane용매HCID 312751,4-Dioxane용매

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온도
90 °C

실험 절차

1,4-dioxane (250 mL) was degassed by purging with N2 gas for 30 min and to this, were added a solution of compound 2 (13.2 g, 53.4 mmol) in 1,4-dioxane (50 mL; degassed), (4-methoxyphenyl)methanethiol (PMBSH) (8.2 g, 53.4 mmol), xantphos (1.54 g, 2.66 mmol), diisopropyl ethyl amine (19.6 mL, 106.8 mmol) and Pd2(dba)3 (1.22 g, 1.33 mmol) at RT. The reaction mixture was heated to 90° C. and stirred for 2 h. The reaction was monitored by TLC; after completion of the reaction, the reaction mixture was diluted with hexane (450 mL) and stirred at RT for 15 min. The resultant solution was filtered through celite and washed with hexane (100 mL). The filtrate was washed water (250 mL) dried over Na2SO4, filtered and concentrated under reduced pressure to obtain the crude. This was purified by silica gel column chromatography using 3-4% EtOAc/Hexanes to afford compound 3 (15 g, 88%) as pale yellow solid. 1H NMR (500 MHz, CDCl3): δ 7.78-7.74 (m, 1H), 7.43-7.39 (m, 1H), 7.19 (d, J=8.0 Hz, 2H), 7.07-7.04 (m, 1H), 6.80 (d, J=8.0 Hz, 2H), 4.41 (q, J=7.2 Hz, 2H), 4.08 (s, 2H), 3.78 (s, 3H), 1.41 (t, J=7.2 Hz, 3H). LC-MS (ESI): 89.7%; m/z 318.9 (M−H+); (column: X Select CSH C-18, 50×3.0 mm, 3.5 μm); RT 4.22 min; 5 mM NH4OAc: ACN; 0.8 mL/min).

후처리

  1. custom1,4-dioxane (250 mL) was degassed
  2. customby purging with N2 gas for 30 min
  3. customafter completion of the reaction
  4. stirringstirred at RT for 15 min
  5. filtrationThe resultant solution was filtered through celite
  6. washwashed with hexane (100 mL)
  7. washThe filtrate was washed water (250 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto obtain the crude
  12. customThis was purified by silica gel column chromatography

출처 및 근거

ORD 기록
ord-119480f1151e48d183adb6be9e7e1f45
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09334261B2

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