Triethylamine → Methanesulfonic acid 2-azido-1-(2-bromo-5-fluoro-pyridin-4-yl)-1-methyl-ethyl ester

HRID 474082Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 474082
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[N:6]([CH2:9][C:10]([C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Br:20])[CH:14]=1)([OH:12])[CH3:11])=[N+:7]=[N-:8].CCN(CC)CC>C(Cl)Cl>[N:6]([CH2:9][C:10]([O:12][S:2]([CH3:1])(=[O:4])=[O:3])([C:13]1[C:18]([F:19])=[CH:17][N:16]=[C:15]([Br:20])[CH:14]=1)[CH3:11])=[N+:7]=[N-:8]

Komponenten

5

Edukt 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 866680521-Azido-2-(2-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol

Produkt 1

HCID 86668053Methanesulfonic acid 2-azido-1-(2-bromo-5-fluoro-pyridin-4-yl)-1-methyl-ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

At 0° C., methanesulfonyl chloride (2.04 ml, 3.00 g, 26.20 mmol) was dropwise added to a solution of 1-azido-2-(2-bromo-5-fluoro-pyridin-4-yl)-propan-2-ol (6.00 g, 21.81 mmol) and NEt3 (3.65 ml, 2.65 g, 26.2 mmol) in DCM (200 ml). The reaction mixture was stirred at 0° C. for 1 h, then for another 1 h at 0° C. to rt. The reaction mixture was quenched with 1M aq. NaHCO3 soln. and diluted with DCM. The phases were separated and the aq. phase was twice reextracted with DCM. The combined org. phases were dried over Na2SO4, filtered and concentrated. HPLC purification (Alltech Grom Saphir 65 Si 10 μM column, 250×50 mm, gradient n-heptane:EtOAc 0-1.6 min 85:15, 1.6-16 min 0:100, 16-21.2 min 0:100, flow 100 ml/min, detection 254 nm) yielded the title compound as well as recovered starting material that could be reacted again according to the above procedure. HPLC RtH4=0.96 min; ESIMS: 353, 355 [(M+H)+]; 1H NMR (400 MHz, CDCl3): δ 8.28 (d, 1H), 7.56 (d, 1H), 4.08 (d, 1H), 3.82 (d, 1H), 3.22 (s, 3H), 2.13 (s, 3H).

Aufarbeitung

  1. waitfor another 1 h at 0° C. to rt
  2. customThe reaction mixture was quenched with 1M aq. NaHCO3 soln
  3. additionand diluted with DCM
  4. customThe phases were separated
  5. dry with materialphases were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customHPLC purification (Alltech Grom Saphir 65 Si 10 μM column, 250×50 mm, gradient n-heptane:EtOAc 0-1.6 min 85:15, 1.6-16 min 0:100, 16-21.2 min 0:100, flow 100 ml/min, detection 254 nm)

Quellen und Nachweise

ORD-Eintrag
ord-91b2928d510141ebae97ecb0b64931ce
Quelldatensatz
uspto-grants-2014_01
Patentnummer
US08637508B2

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