Potassium Hydroxide → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4,4'-difluoro-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1994623Notes

Reaction equation

HRID 1994623 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[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[F:31][C:32]1[C:37]([CH:38]([CH3:40])[CH3:39])=[CH:36][C:35](B(O)O)=[C:34]([O:44][CH3:45])[CH:33]=1.[OH-].[K+]>O1CCOCC1.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[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[CH:25]=[C:24]([F:26])[CH:23]=[CH:22][C:21]=3[C:35]3[CH:36]=[C:37]([CH:38]([CH3:40])[CH3:39])[C:32]([F:31])=[CH:33][C:34]=3[O:44][CH3:45])[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1

Participants

6

Reactant 3

HCID 14797Potassium HydroxideHCID 53363739(4-Fluoro-5-isopropyl-2-methoxyphenyl)boronic acidHCID 59135189(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 11664298(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4,4'-difluoro-5'-isopropyl-2'-methoxybiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-(2-bromo-5-fluorobenzyl)-4-methyl-1,3-oxazolidin-2-one (1.0 g, 2.0 mmol) in 1,4-dioxane (6 mL) was added (4-fluoro-5-isopropyl-2-methoxyphenyl)boronic acid (509 mg, 2.4 mmol), [1,1′-bis(diphenylphosphino) ferrocene] dichloropalladium (II) (82 mg, 5 mol %) and aq. potassium hydroxide (1.3 mL, 3M, 2 eq.). The reaction mixture was purged with nitrogen and then sealed in a microwave vessel. The reaction vessel was subject to microwave irradiation at 150° C. for 40 min. Crude mixture was worked up with water. Volatiles were evaporated. The resulting mixture was extracted with EtOAc. The combined extracts were dried over Na2SO4. The resulting purple residue was purified by SiO2 (Biotage 40+M cartridge, eluted by EtOAc/hexane, gradient; 5% to 25%). The titled compound was obtained as clear solid. LC-MS:588.23 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 6:4 mixture of rotamers δ 7.85 (s, 1H), 7.69 (s, 2H), 7.16-7.21 (m, 1.5H), 7.04-7.13 (m, 1.5H), 6.96 (dd, J=14.3, 8.80 Hz, 1H), 6.65 (d, J=10.0 Hz, 1H), 5.59 (d, J=8.0 Hz, 0.6H), 5.43 (d, J=8.0 Hz, 0.4H), 4.85 (d, J=15.8 Hz, 0.6H), 4.82 (d, J=15.8 Hz, 0.4H), 4.02 (d, J=15.8 Hz, 0.6H), 3.85 (m, 0.6H), 3.76-3.81 (m, 0.8H), 3.75 (s, 1.8H), 3.73 (s, 1.2H), 3.19 (m, 1H), 1.14-1.26 (m, 6H), 0.56 (d, J=6.6 Hz, 1.2H), 0.38 (d, J=6.6 Hz, 1.8H).

Workup

  1. customThe reaction mixture was purged with nitrogen
  2. customsealed in a microwave vessel
  3. customirradiation at 150° C. for 40 min
  4. customVolatiles were evaporated
  5. extractionThe resulting mixture was extracted with EtOAc
  6. dry with materialThe combined extracts were dried over Na2SO4
  7. customThe resulting purple residue was purified by SiO2 (Biotage 40+M cartridge, eluted by EtOAc/hexane, gradient; 5% to 25%)

Sources & evidence

ORD record
ord-b0487bbc190446a08e7c06915dfc6bb3
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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