Water → (S)-methyl 2-(tert-butoxy)-2-(4-(4-(difluoromethyl)phenyl)-2-methyl-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate

HRID 2406402노트

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HRID 2406402 반응식
[F:1][CH:2]([F:18])[C:3]1[CH:8]=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].O.[C:28]([O:32][C@@H:33]([C:38]1[C:39](I)=[C:40]2[C:47]3[CH2:48][CH2:49][CH2:50][CH2:51][C:46]=3[S:45][C:41]2=[N:42][C:43]=1[CH3:44])[C:34]([O:36][CH3:37])=[O:35])([CH3:31])([CH3:30])[CH3:29]>O1CCOCC1.[Pd+2].ClC1C=C[C-](P(C(C)(C)C)C(C)(C)C)C=1Cl.[C-]1(P(C(C)(C)C)C(C)(C)C)C=CC=C1.[Fe+2]>[C:28]([O:32][C@@H:33]([C:38]1[C:39]([C:6]2[CH:5]=[CH:4][C:3]([CH:2]([F:1])[F:18])=[CH:8][CH:7]=2)=[C:40]2[C:47]3[CH2:48][CH2:49][CH2:50][CH2:51][C:46]=3[S:45][C:41]2=[N:42][C:43]=1[CH3:44])[C:34]([O:36][CH3:37])=[O:35])([CH3:31])([CH3:29])[CH3:30]

참가 물질

7

반응물 4

HCID 962WaterHCID 62657Potassium Phosphate, TribasicHCID 584525412-(4-(DifluoroMethyl)phenyl)-4,4,5,5-tetraMethyl-1,3,2-dioxaborolaneHCID 69673123Methyl (2S)-tert-butoxy(4-iodo-2-methyl-5,6,7,8-tetrahydro[1]benzothieno[2,3-b]pyridin-3-yl)acetate

생성물 1

HCID 67607847(S)-methyl 2-(tert-butoxy)-2-(4-(4-(difluoromethyl)phenyl)-2-methyl-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate수율 85.4%

시약·촉매·용매 2

HCID 178454866HCID 178454866, 화합물촉매HCID 312751,4-Dioxane용매

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온도
100 °C

실험 절차

2-(4-(Difluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (1.04 g, 4.09 mmol), potassium phosphate (1.35 g, 6.36 mmol), water (750 μL) and dichloro [1,1′ bis(di-tert-butylphosphino)]ferrocene palladium (II)™ (101 mg, 155 μmol) were added to a stirred solution of (S)-methyl 2-(tert-butoxy)-2-(4-iodo-2-methyl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate (750 mg, 1.58 mmol) in dioxane (11 mL) in a reaction tube. The reaction mixture was degassed with argon for 2 minutes, sealed and then stirred at 100° C. for 16 hours. The reaction mixture was cooled to room temperature, diluted with ethyl acetate (30 mL) and water (30 mL) and then passed through a pad of celite. The layers of the filtrate were separated and the aqueous layer was extracted with ethyl acetate (3×30 mL). The combined organic layers were dried (Na2SO4) and concentrated in vacuo to yield the crude product. The residue was purified by flash column chromatography eluting with ethyl acetate in heptane (10%) to give the title compound (639 mg, 85%) as a yellow oil. 1H NMR (400 MHz, CDCl3) δ=0.96 (s, 9H), 1.85-1.35 (m, 6H), 2.72 (s, 3H), 2.85-2.75 (m, 2H), 3.67 (s, 3H), 4.95 (s, 1H), 6.76 (t, 1H), 6.45 (d, 1H), 7.61-7.51 (m, 3H). LCMS (run time=5 minutes, basic): Rt=3.37 minutes; m/z 474.23 [M+H+].

후처리

  1. customThe reaction mixture was degassed with argon for 2 minutes
  2. customsealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate (30 mL) and water (30 mL)
  5. customThe layers of the filtrate were separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (3×30 mL)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. concentrationconcentrated in vacuo
  9. customto yield the crude product
  10. customThe residue was purified by flash column chromatography
  11. washeluting with ethyl acetate in heptane (10%)

출처 및 근거

ORD 기록
ord-fcf91a6c0e054be39edbaad140cf7b57
출처 데이터셋
uspto-grants-2014_08
특허 번호
US08809363B2

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