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 2406404Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2406404
[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]

Komponenten

8

Edukt 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

Produkt 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)acetateAusbeute 72,7 %

Reagenzien, Katalysatoren, Lösungsmittel 4

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel2×HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

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+].

Aufarbeitung

  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%)

Quellen und Nachweise

ORD-Eintrag
ord-389a15606f2e402db8f7911e8451e24e
Quelldatensatz
uspto-grants-2014_08
Patentnummer
US08809363B2

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