Sodium Carbonate → (4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

HRID 1500299Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1500299
Br[C:2]1[CH:3]=[CH:4][C:5]([C:8]2(F)[CH2:11][S:10](=[O:13])(=[O:12])[CH2:9]2)=[N:6][CH:7]=1.[C:15]([O:19][C:20]([N:22]1[C@H:26]([CH2:27][F:28])[C@@H:25]([C:29]2[CH:34]=[CH:33][C:32](B3OC(C)(C)C(C)(C)O3)=[CH:31][CH:30]=2)[O:24][C:23]1([CH3:45])[CH3:44])=[O:21])([CH3:18])([CH3:17])[CH3:16].C(=O)([O-])[O-].[Na+].[Na+]>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.C1(C)C=CC=CC=1.C(O)C.O>[O:12]=[S:10]1(=[O:13])[CH:11]=[C:8]([C:5]2[N:6]=[CH:7][C:2]([C:32]3[CH:31]=[CH:30][C:29]([C@H:25]4[O:24][C:23]([CH3:44])([CH3:45])[N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[C@@H:26]4[CH2:27][F:28])=[CH:34][CH:33]=3)=[CH:3][CH:4]=2)[CH2:9]1

Komponenten

6

Edukt 3

HCID 10340Sodium CarbonateHCID 58631114(4S,5R)-Rel-tert-butyl4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidine-3-carboxylateHCID 867131853-(5-Bromopyridin-2-yl)-3-fluorothietane 1,1-dioxide

Produkt 1

HCID 86713187(4S,5R)-tert-butyl 5-(4-(6-(1,1-dioxido-2H-thiet-3-yl)pyridin-3-yl)phenyl)-4-(fluoromethyl)-2,2-dimethyloxazolidine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 86587398Ethanol toluene waterLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

The solution of the product of step 3, Example 18 (0.15 g, 0.538 mmol, 1 eq), (4S,5R)-4-Fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidine-3-carboxylic acid tert-butyl ester (previously described in US2004082553, Example 20, intermediate 19, 0.234 g, 0.538 mmol, 1 eq) and sodium carbonate (0.171 g, 1.613 mmol, 3 eq) in mixture of Toluene/Ethanol/Water (1:1:0.5, 2.5 mL) is degassed with nitrogen for 30 minutes in sealed tube. To the resulting reaction mixture tetrakis(triphenylphosphine)palladium(0) (0.062 g, 0.054 mmol, 0.1 eq) is added. Resulting reaction mixture is heated at 80° C. for 6 hours. The reaction mixture is quenched with water (15 mL) and extracted with ethyl acetate (3×25 mL). Combined organic layer is dried over sodium sulphate and concentrated in vacuo. The crude compound is purified by column chromatography using (100-200 mesh silica). Desired compound is eluted with 30% ethyl acetate in hexane to afford title compound as yellow solid (0.16 g): 1H-NMR (400 MHz, DMSO) δ: 1.43 (bs, 9H), 1.51 (s, 3H), 1.64 (s, 3H), 3.85-3.90 (m, 1H), 4.47-4.59 (m, 1H), 4.75-4.84 (m, 1H), 5.05 (s, 2H), 5.15 (d, 1H, J=7.16 Hz), 7.62 (d, 2H, J=8.12 Hz), 7.76 (s, 1H), 7.87 (d, 2H, J=8.2 Hz), 7.93 (d, 1H, J=8.12 Hz), 8.31-8.34 (dd, 1H, J1=8.24 Hz, J2=2.16 Hz). 9.07 (d, 1H, J=1.88 Hz). LC-MS (m/z): [M+H] 489.1.

Aufarbeitung

  1. customis degassed with nitrogen for 30 minutes in sealed tube
  2. additionis added
  3. customResulting
  4. customreaction mixture
  5. customThe reaction mixture is quenched with water (15 mL)
  6. extractionextracted with ethyl acetate (3×25 mL)
  7. dry with materialCombined organic layer is dried over sodium sulphate
  8. concentrationconcentrated in vacuo
  9. customThe crude compound is purified by column chromatography
  10. washDesired compound is eluted with 30% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-092e41b5151449aca5db6bb7b359ffc3
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206126B2

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