3-Fluoroazetidine → HCID 86704653, compound

HRID 1508605Notes

Reaction equation

HRID 1508605 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]3[C:24]([C:25]4[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[C:28]([F:34])=[CH:27][C:26]=4[O:35][CH3:36])=[CH:23][N:22]=[C:21](S(C)(=O)=O)[N:20]=3)[C@H:13]2[CH3:41])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1.[F:42][CH:43]1[CH2:46][NH:45][CH2:44]1>C1COCC1.CCOC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([C@H:12]2[O:16][C:15](=[O:17])[N:14]([CH2:18][C:19]3[C:24]([C:25]4[CH:30]=[C:29]([CH:31]([CH3:33])[CH3:32])[C:28]([F:34])=[CH:27][C:26]=4[O:35][CH3:36])=[CH:23][N:22]=[C:21]([N:45]4[CH2:46][CH:43]([F:42])[CH2:44]4)[N:20]=3)[C@H:13]2[CH3:41])[CH:5]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:7]=1

Participants

5

Reactant 2

HCID 36035423-FluoroazetidineHCID 86704654HCID 86704654, compound

Product 1

HCID 86704653HCID 86704653, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

To (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-3-({5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]-2-(methylsulfonyl)pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (175 mg, 0.265 mmol) in THF (1 mL) was added TEA (0.369 mL, 2.65 mmol) and 3-fluoroazetidine (236 mg, 2.120 mmol). The reaction was capped and heated at 100° C. for 10 min by microwave irradiation. The reaction was diluted with EtOAc, washed with sat. aqueous NaHCO3, water and brine. The organic phase was dried over sodium sulfate, filtered and concentrated before purification by column chromatography to afford (4S,5R)-5-[3-bromo-5-(trifluoromethyl)phenyl]-3-({2-(3-fluoroazetidin-1-yl)-5-[4-fluoro-2-methoxy-5-(propan-2-yl)phenyl]pyrimidin-4-yl}methyl)-4-methyl-1,3-oxazolidin-2-one (160 mg, 0.244 mmol). LCMS calc.=655.2/657.2. found=655.4/657.4.

Workup

  1. customThe reaction was capped
  2. washwashed with sat. aqueous NaHCO3, water and brine
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated before purification by column chromatography

Sources & evidence

ORD record
ord-3f28176fd012488885ffdc5204615bc2
Source dataset
uspto-grants-2015_12
Patent number
US09221834B2

Reaction notes

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