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

HRID 2406404ノート

反応式

HRID 2406404 の反応式
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:8]=[CH:7][C:6](B2OC(C)(C)C(C)(C)O2)=[CH:5][CH:4]=1.C(N(C(C)C)C(C)C)C.[C:29]([O:33][C@@H:34]([C:39]1[C:40](I)=[C:41]2[C:48]3[CH2:49][CH2:50][CH2:51][CH2:52][C:47]=3[S:46][C:42]2=[N:43][C:44]=1[CH3:45])[C:35]([O:37][CH3:38])=[O:36])([CH3:32])([CH3:31])[CH3:30]>O1CCOCC1.C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:29]([O:33][C@@H:34]([C:39]1[C:40]([C:6]2[CH:5]=[CH:4][C:3]([C:2]([F:1])([F:18])[F:19])=[CH:8][CH:7]=2)=[C:41]2[C:48]3[CH2:49][CH2:50][CH2:51][CH2:52][C:47]=3[S:46][C:42]2=[N:43][C:44]=1[CH3:45])[C:35]([O:37][CH3:38])=[O:36])([CH3:32])([CH3:30])[CH3:31]

参加物

8

反応物 3

HCID 81531DiisopropylethylamineHCID 27606054,4,5,5-Tetramethyl-2-(4-(trifluoromethyl)phenyl)-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 67607979(S)-methyl 2-(tert-butoxy)-2-(2-methyl-4-(4-(trifluoromethyl)phenyl)-5,6,7,8-tetrahydro benzo[4,5]thieno[2,3-b]pyridin-3-yl)acetate収率 72.7%

試薬・触媒・溶媒 4

HCID 178418397HCID 178418397、化合物触媒HCID 962Water溶媒2 回HCID 8857Ethyl Acetate溶媒HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

2-(4-(Trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (115 g, 0.42 mmol), N-ethyl-N-isopropylpropan-2-amine (120 μL, 0.64 mmol) and water (500 μL) 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 (100 mg, 0.21 mmol) in dioxane (2 mL) in a reaction tube. The reaction mixture was degassed with argon for 2 minutes, then tetrakis(triphenylphosphine)palladium(0) (25 mg, 21 μmol) was added and the vessel was sealed and heated at 100° C. for 16 hours. The reaction mixture was cooled to room temperature and diluted with ethyl acetate (30 mL) and water (30 mL) and the mixture was passed through a pad of celite. The layers of the filtrate were separated and the organic layer was washed with brine (30 mL), dried (MgSO4) and concentrated in vacuo to yield the crude product as a brown gum. The residue was purified by flash column chromatography eluting with ethyl acetate in heptane (10%) to give the title compound (75 mg, 72%) 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), 3.69 (s, 3H), 4.91 (s, 1H), 7.40 (d, 1H), 7.61 (d, 1H), 7.71 (m, 2H). LCMS (run time=5 minutes, basic): Rt=3.64 minutes; m/z 492.06 [M+H+].

後処理

  1. customThe reaction mixture was degassed with argon for 2 minutes
  2. customthe vessel was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe layers of the filtrate were separated
  5. washthe organic layer was washed with brine (30 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated in vacuo
  8. customto yield the crude product as a brown gum
  9. customThe residue was purified by flash column chromatography
  10. washeluting with ethyl acetate in heptane (10%)

出典と根拠

ORDレコード
ord-389a15606f2e402db8f7911e8451e24e
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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