Bromoform → (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

HRID 1994629Notes

Reaction equation

HRID 1994629 reaction equation
N[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[C:11]([F:17])=[CH:10][C:9]=2[O:18][CH3:19])=[C:4]([CH2:20][N:21]2[C@@H:25]([CH3:26])[C@@H:24]([C:27]3[CH:32]=[C:31]([C:33]([F:36])([F:35])[F:34])[CH:30]=[C:29]([C:37]([F:40])([F:39])[F:38])[CH:28]=3)[O:23][C:22]2=[O:41])[CH:3]=1.N(OC(C)(C)C)=O.C(Br)(Br)[Br:50]>>[F:39][C:37]([F:38])([F:40])[C:29]1[CH:28]=[C:27]([C@H:24]2[O:23][C:22](=[O:41])[N:21]([CH2:20][C:4]3[CH:3]=[C:2]([Br:50])[CH:7]=[CH:6][C:5]=3[C:8]3[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[C:11]([F:17])=[CH:10][C:9]=3[O:18][CH3:19])[C@H:25]2[CH3:26])[CH:32]=[C:31]([C:33]([F:35])([F:36])[F:34])[CH:30]=1

Participants

4

Reactant 3

HCID 5558BromoformHCID 10906Tert-Butyl nitriteHCID 11614021(4S,5R)-3-[(4-amino-4'-fluoro-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 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-one

Conditions

Temperature
80 °C

Procedure

To a solution (4S,5R)-3-[(4-amino-4′-fluoro-5′-isopropyl-2′-methoxybiphenyl-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (526 mg, 0.90 mmol) in bromoform (2.5 mL) was added tert-butyl nitrite (186 mg, 1.80 mmol). The resulting mixture was stirred at 80° C. for 20 min. An aliquot indicated completion of the reaction. The reaction crude was purified silica gel to afford the title compound as a yellow glass. LC-MS: 650.09 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 1:1 mixture of rotamers δ 7.85 (s, 1H), 7.69 (s, 2H), 7.60 (s, 0.5H), 7.48-7.53 (m, 1.5H), 7.07-7.11 (m, 1H), 6.93-6.99 (m, 1H), 6.62-6.67 (m, 1H), 5.59 (d, J=8.0 Hz, 0.5H), 5.39 (d, J=7.0 Hz, 0.5H), 4.82 (d, J=6.5 Hz, 0.5H), 4.75 (d, J=6.5 Hz, 0.5H), 3.98 (d, J=16.0 Hz, 0.5H), 3.76-3.85 (m, 1.5H), 3.75 (s, 1.5H), 3.74 (s, 1.5H), 3.13-3.23 (m, 1H), 1.13-1.29 (m, 6H), 0.52 (d, J=6.5 Hz, 1.5H), 0.34 (d, J=7.0 Hz, 1.5H).

Workup

  1. customcompletion of the reaction
  2. customThe reaction crude
  3. customwas purified silica gel

Sources & evidence

ORD record
ord-4a613e7cce7946aeae084d4b6174ff42
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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