반응 #1115847

반응 방정식

N2

(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

copper(I) cyanide

→

titled compound

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

용매

N,N-dimethylformamide

반응 조건

후처리

1. 1
   기타The resulting reaction mixture
2. 2
   기타purged
3. 3
   기타sealed in a microwave vessel
4. 4
   기타irradiation at 150° C. for 30 min
5. 5
   기타microwave irradiation at 150° C. for 30 min
6. 6
   기타was formed
7. 7
   기타all starting bromide was consumed
8. 8
   기타Reaction crude
9. 9
   기타was partitioned between water and hexanes
10. 10
    추출The aqueous phase was back extracted with diethyl ether
11. 11
    건조The combined extracts were dried over Na2SO4

실험 절차

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) δ 1:1 mixture of rotamers δ 7.86 (s, 1 H), 7.61 (S, 0.5 H), 7.67-7.71 (m, 2.5H), 7.64-7.68 (m, 1 H), 7.32-7.36 (m, 1 H), 6.98 (d, J=8.5 Hz, 0.5H), 6.95 (d, J=8.5 Hz, 0.5 H), 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, 0.5 H), 4.06 (d, J=16 Hz, 0.5 H), 3.79-3.86 (m, 1 H), 3.70-3.78 (m, 3.5 H), 3.16-3.24 (m, 1H), 3.75 (s, 1.5 H), 3.16-3.25 (m, 1H), 3.14 (s, 1.5 H), 3.13 (s, 1.5 H), 1.15-1.27 (m, 6 H), 0.54 (d, J=7.0 Hz, 1.5 H), 0.37 (d, J=6.5 Hz, 1.5 H).

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