Tetrahydrofuran → (4S,5R)-3-[(6-azetidin-1-yl-3-bromo-4-methylpyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1508507Notes

Reaction equation

HRID 1508507 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[C:25]([Br:26])=[C:24]([CH3:27])[CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:29])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.C1COCC1.[NH:37]1[CH2:40][CH2:39][CH2:38]1>>[N:37]1([C:22]2[N:21]=[C:20]([CH2:19][N:15]3[C@@H:14]([CH3:29])[C@@H:13]([C:5]4[CH:4]=[C:3]([C:2]([F:31])([F:30])[F:1])[CH:8]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:6]=4)[O:17][C:16]3=[O:18])[C:25]([Br:26])=[C:24]([CH3:27])[CH:23]=2)[CH2:40][CH2:39][CH2:38]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 10422AzetidineHCID 86704597(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloro-4-methylpyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704599(4S,5R)-3-[(6-azetidin-1-yl-3-bromo-4-methylpyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Conditions

Temperature
150 °C

Procedure

In a microwave tube, (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloro-4-methylpyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (500 mg, 0.940 mmol) was dissolved in a 2M solution of azetidine in THF (8 mL, 16.0 mmol). The tube was sealed and the reaction was heated to 150° C. for 2 hr in the microwave. The reaction was then cooled and concentrated. The residue was purified via flash chromatography on silica gel (0 to 75% ethyl acetate/hexanes) to afford (4S,5R)-3-[(6-azetidin-1-yl-3-bromo-4-methylpyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS=551.9 and 553.9 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 7.87 (s, 1H), 7.77 (s, 2H), 6.09 (s, 1H), 5.77 (d, J=8.7 Hz, 1H), 4.87 (d, J=17.2 Hz, 1H), 4.37 (m, 1H), 4.21 (d, J=16.9 Hz, 1H), 3.99 (m, 4H), 2.38 (m, 2H), 2.30 (s, 3H), 0.77 (d, J=6.7 Hz, 3H).

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction was then cooled
  3. concentrationconcentrated
  4. customThe residue was purified via flash chromatography on silica gel (0 to 75% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f77d13361f514a55b2a10bcd2ee73608
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

Loading…