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

HRID 1508506Notes

Reaction equation

HRID 1508506 reaction equation
[F:1][C:2]([F:30])([F:29])[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])=[CH:24][CH:23]=[C:22](Cl)[N:21]=3)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[NH:31]1[CH2:34][CH2:33][CH2:32]1.C1COCC1>>[N:31]1([C:22]2[N:21]=[C:20]([CH2:19][N:15]3[C@@H:14]([CH3:28])[C@@H:13]([C:5]4[CH:4]=[C:3]([C:2]([F:30])([F:29])[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])=[CH:24][CH:23]=2)[CH2:34][CH2:33][CH2:32]1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 10422AzetidineHCID 57576268(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 86704598(4S,5R)-3-[(6-azetidin-1-yl-3-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Conditions

Temperature
150 °C

Procedure

To a microwave tube containing (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(3-bromo-6-chloropyridin-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (330 mg, 0.637 mmol) was added a 2M solution of azetidine in THF (4 mL, 8 mmol). The tube was sealed and the reaction was heated at 150° C. for 30 minutes in the microwave. The reaction was 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-bromopyridin-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one. LCMS=537.9 and 539.8 (M+H)+. 1H NMR (CDCl3, 500 MHz) δ 7.88 (s, 1H), 7.78 (s, 2H), 7.51 (d, J=8.6 Hz, 1H), 6.10 (d, J=8.7 Hz, 1H), 5.77 (d, J=8.6 Hz, 1H), 4.86 (d, J=17.0 Hz, 1H), 4.35 (m, 1H), 4.20 (d, J=16.9 Hz, 1H), 4.01 (m, 4H), 2.40 (m, 2H), 0.78 (d, J=6.7 Hz, 3H).

Workup

  1. customThe tube was sealed
  2. temperatureThe reaction was 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-ddb35cca52064d0f82e928da52e8feaf
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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