Nitrogen → 2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-4-carbonitrile

HRID 1994632Notes

Reaction equation

HRID 1994632 reaction equation
[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24](Br)[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=3[O:37][CH3:38])[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[Cu][C:43]#[N:44].N#N>CN(C)C=O>[F:1][C:2]([F:41])([F:40])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([C:43]#[N:44])[CH:23]=[CH:22][C:21]=3[C:27]3[CH:32]=[C:31]([CH:33]([CH3:35])[CH3:34])[C:30]([F:36])=[CH:29][C:28]=3[O:37][CH3:38])[C@H:14]2[CH3:39])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

5

Reactant 3

HCID 947NitrogenHCID 11556473(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl)-3-[(4-bromo-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-oneHCID 178418546HCID 178418546, compound

Product 1

HCID 117069992-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-4-carbonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-4′-fluoro-5′-isopropyl-2′-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.15 mmol) in N,N-dimethylformamide (1.5 mL) was added copper(I) cyanide (17 mg, 0.19 mmol). The resulting reaction mixture was N2 purged and sealed in a microwave vessel. The vessel was subject to microwave irradiation at 150° C. for 30 min. LC-MS indicated only the starting bromide was present. Added tetrakis(triphenylphosphine)palladium(0) (10 mg, 6 mol %) into the reaction mixture. Repeated microwave irradiation at 150° C. for 30 min. An aliquot indicated the desired product was formed and all starting bromide was consumed. Reaction crude was partitioned between water and hexanes. The aqueous phase was back extracted with diethyl ether. The combined extracts were dried over Na2SO4. The titled compound was obtained as a glassy material after two preparative TLC plates developed respectively by 20% EtOAc in hexanes and 4% EtOAc in dichloromethane. LC-MS: 595.03 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 1:1 mixture of rotamers δ 7.86 (s, 1H), 7.61 (S, 0.5H), 7.67-7.71 (m, 2.5H), 7.64-7.68 (m, 1H), 7.32-7.36 (m, 1H), 6.98 (d, J=8.5 Hz, 0.5H), 6.95 (d, J=8.5 Hz, 0.5H), 6.68 (d, J=12 Hz, 1H), 5.62 (d, J=8.0 Hz, 0.5H), 5.46 (d, J=8.0 Hz, 0.5H), 4.85 (d, J=16.0 Hz, 0.5H), 4.80 (d, J=16.0 Hz, 0.5H), 4.06 (d, J=16 Hz, 0.5H), 3.79-3.86 (m, 1H), 3.70-3.78 (m, 3.5H), 3.16-3.24 (m, 1H), 3.75 (s, 1.5H), 3.16-3.25 (m, 1H), 3.14 (s, 1.5H), 3.13 (s, 1.5H), 1.15-1.27 (m, 6H), 0.54 (d, J=7.0 Hz, 1.5H), 0.37 (d, J=6.5 Hz, 1.5H).

Workup

  1. customThe resulting reaction mixture
  2. custompurged
  3. customsealed in a microwave vessel
  4. customirradiation at 150° C. for 30 min
  5. custommicrowave irradiation at 150° C. for 30 min
  6. customwas formed
  7. customall starting bromide was consumed
  8. customReaction crude
  9. customwas partitioned between water and hexanes
  10. extractionThe aqueous phase was back extracted with diethyl ether
  11. dry with materialThe combined extracts were dried over Na2SO4

Sources & evidence

ORD record
ord-18f5ddc721c0414aa9e34b8f06007191
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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