Dichloromethane → (5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester

HRID 1520555Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1520555
[F:1][CH:2]([F:29])[C:3]([N:5]1[C@H:9]([CH2:10][F:11])[C@@H:8]([C:12]2[CH:17]=[CH:16][C:15](B3OC(C)(C)C(C)(C)O3)=[CH:14][CH:13]=2)[O:7][C:6]1([CH3:28])[CH3:27])=[O:4].[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:43]=[CH:42][C:41](Cl)=[CH:40][N:39]=1)([CH3:33])([CH3:32])[CH3:31].C([O-])([O-])=O.[K+].[K+].C(Cl)Cl>C(O)(C)C.O>[C:30]([O:34][C:35](=[O:45])[NH:36][CH2:37][C:38]1[N:43]=[CH:42][C:41]([C:15]2[CH:16]=[CH:17][C:12]([C@H:8]3[O:7][C:6]([CH3:27])([CH3:28])[N:5]([C:3](=[O:4])[CH:2]([F:29])[F:1])[C@@H:9]3[CH2:10][F:11])=[CH:13][CH:14]=2)=[CH:40][N:39]=1)([CH3:33])([CH3:31])[CH3:32]

Komponenten

6

Edukt 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 72710400tert-Butyl ((5-chloropyrimidin-2-yl)methyl)carbamateHCID 866954142,2-difluoro-1-((4S,5R)-4-(fluoromethyl)-2,2-dimethyl-5-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)oxazolidin-3-yl)ethanone

Produkt 1

HCID 86695517(5-{4-[(4S,5R)-3-(2,2-Difluoro-acetyl)-4-fluoromethyl-2,2-dimethyl-oxazolidin-5-yl]-phenyl}-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl esterAusbeute 36,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 21889133Propan-2-ol--water (1/1)Lösungsmittel

Reaktionsbedingungen

Temperatur
140 °C

Versuchsvorschrift

To a stirred solution of 2,2-Difluoro-1-{(4S,5R)-4-fluoromethyl-2,2-dimethyl-5-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-oxazolidin-3-yl}-ethanone (0.286 g, 0.694 mmol) and (5-Chloro-pyrimidin-2-ylmethyl)-carbamic acid tert-butyl ester (0.2 g, 0.694 mmol) in isopropylalcohol:water (2:1, 6 mL) is added K2CO3 (0.287 g, 2.083 mmol) at room temperature. Resulting reaction mixture is degassed with nitrogen for 20 minutes followed by addition of Pd(dppf)Cl2.CH2Cl2 (0.028 g, 0.035 mmol). The resulting reaction mixture is heated to 140° C. for 20 minutes in a microwave. Solvent is evaporated in vacuo and the crude material is diluted using water and extracted with ethyl acetate. Organic layer is dried over sodium sulphate, concentrated and purified by column chromatography using Combi-flash eluting with 75% ethyl acetate in hexane to afford the title compound (0.125 g): 1H NMR (400 MHz, DMSO-d6) δ: 1.40 (s, 9H), 1.52 (s, 3H), 1.60 (s, 3H), 4.36 (d, J=6.16 Hz, 2H), 4.54-4.58 (m, 0.5H), 4.66-4.73 (m, 1H), 4.82-4.85 (m, 0.5H), 4.91-4.95 (m, 1H), 5.28 (d, J=3.52 Hz, 1H), 6.64 (t, J=52.44 Hz, 1H), 7.32 (t, J=6.04 Hz, 1H), 7.62 (d, J=8.04 Hz, 2H), 7.86 (d, J=8.04 Hz, 2H), 9.10 (s, 2H). LC-MS (m/z): [M+H]=495.

Aufarbeitung

  1. customResulting
  2. customreaction mixture
  3. customis degassed with nitrogen for 20 minutes
  4. additionfollowed by addition of Pd(dppf)Cl2
  5. customThe resulting reaction mixture
  6. customSolvent is evaporated in vacuo
  7. additionthe crude material is diluted
  8. extractionextracted with ethyl acetate
  9. dry with materialOrganic layer is dried over sodium sulphate
  10. concentrationconcentrated
  11. custompurified by column chromatography
  12. washeluting with 75% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-65498320cffd424386db6ca4d177922b
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09073894B2

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