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 2406402ノート

反応式

HRID 2406402 の反応式
[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]

参加物

7

反応物 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

生成物 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)acetate収率 85.4%

試薬・触媒・溶媒 2

HCID 178454866HCID 178454866、化合物触媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

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+].

後処理

  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%)

出典と根拠

ORDレコード
ord-fcf91a6c0e054be39edbaad140cf7b57
出典データセット
uspto-grants-2014_08
特許番号
US08809363B2

反応ノート

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