Bromoform → (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-2'-chloro-5'-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

HRID 1994641Notes

Reaction equation

HRID 1994641 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])[CH:11]=[CH:10][C:9]=2[Cl:17])=[C:4]([CH2:18][N:19]2[C@@H:23]([CH3:24])[C@@H:22]([C:25]3[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=[C:27]([C:35]([F:38])([F:37])[F:36])[CH:26]=3)[O:21][C:20]2=[O:39])[CH:3]=1.N(OC(C)(C)C)=O.C(Br)(Br)[Br:48]>ClCCl>[F:37][C:35]([F:36])([F:38])[C:27]1[CH:26]=[C:25]([C@H:22]2[O:21][C:20](=[O:39])[N:19]([CH2:18][C:4]3[CH:3]=[C:2]([Br:48])[CH:7]=[CH:6][C:5]=3[C:8]3[CH:13]=[C:12]([CH:14]([CH3:16])[CH3:15])[CH:11]=[CH:10][C:9]=3[Cl:17])[C@H:23]2[CH3:24])[CH:30]=[C:29]([C:31]([F:34])([F:33])[F:32])[CH:28]=1

Participants

5

Reactant 3

HCID 5558BromoformHCID 10906Tert-Butyl nitriteHCID 11570489(4S,5R)-3-[(4-amino-2'-chloro-5'-isopropylbiphenyl-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one

Product 1

HCID 11556418(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[(4-bromo-2'-chloro-5'-isopropylbiphenyl-2-yl)methyl]-4-methyl-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

To a solution of (4S,5R)-3-[(4-amino-2′-chloro-5′-isopropylbiphenyl-2-yl)methyl]-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (100 mg, 0.175 mmol) in bromoform (0.5 mL) and dichloromethane (1 mL) was added t-butyl nitrite (23 μL, d=0.867, 90% pure, 0.193 mmol). The resulting mixture was stirred at 50° C. for 1 h. An aliquot indicated completion of the reaction. The reaction crude was deposited on 2 prep-TLC plates eluted by dichloromethane to afford the title compound. LC-MS: 635.80 (M+1)+. 1H NMR (CDCl3, 500 MHz) a 6:4 mixture of rotamers δ 7.84-7.88 (m, 1H), 7.67-7.74 (m, 2H), 7.60-7.63 (m, 1H), 7.51-7.57 (m, 1H), 7.38-7.42 (m, 1H), 7.19-7.23 (m, 1H), 7.11-7.16 (m, 1H), 7.09 (d, J=2.3 Hz, 0.6H), 7.03 (d, J=2.3 Hz, 0.4H), 5.66 (d, J=8.0 Hz, 0.4H), 5.55 (d, J=8.0 Hz, 0.6H), 4.86 (d, J=15.6 Hz, 0.6H), 4.70 (d, J=15.6 Hz, 0.4H), 3.77-4.00 (m, 2H), 2.87-2.95 (m, 1H), 1.20-1.28 (m, 6H), 0.53 (d, J=6.6 Hz, 1.2H), 0.45 (d, J=6.4 Hz, 1.8H).

Workup

  1. customcompletion of the reaction
  2. customThe reaction crude
  3. washeluted by dichloromethane

Sources & evidence

ORD record
ord-06fd6294560540c18de2b60b80eefa11
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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