Water → HCID 11498105, compound

HRID 1028490Notes

Reaction equation

HRID 1028490 reaction equation
[C:1](Cl)(Cl)=[O:2].[F:5][C:6]([F:44])([F:43])[C:7]1[CH:8]=[C:9]([CH:17]([NH:20][CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:31])([F:30])[F:29])[CH:25]=[CH:24][C:23]=2[C:32]2[CH:37]=[C:36]([CH:38]([CH3:40])[CH3:39])[CH:35]=[CH:34][C:33]=2[O:41][CH3:42])[CH2:18][OH:19])[CH:10]=[C:11]([C:13]([F:16])([F:15])[F:14])[CH:12]=1.CCN(C(C)C)C(C)C.O>C1(C)C=CC=CC=1.C(Cl)Cl>[F:5][C:6]([F:43])([F:44])[C:7]1[CH:8]=[C:9]([CH:17]2[CH2:18][O:19][C:1](=[O:2])[N:20]2[CH2:21][C:22]2[CH:27]=[C:26]([C:28]([F:29])([F:30])[F:31])[CH:25]=[CH:24][C:23]=2[C:32]2[CH:37]=[C:36]([CH:38]([CH3:39])[CH3:40])[CH:35]=[CH:34][C:33]=2[O:41][CH3:42])[CH:10]=[C:11]([C:13]([F:14])([F:15])[F:16])[CH:12]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6371PhosgeneHCID 81531DiisopropylethylamineHCID 86603402HCID 86603402, compound

Product 1

HCID 11498105HCID 11498105, compound

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of phosgene (21 μL of a 20% solution in toluene, ˜0.0535 mmol) in CH2Cl2 (0.5 mL) was added 2-[3,5-bis(trifluoromethyl)phenyl]-2-({[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}amino)ethanol (3.1 mg, 0.00535 mmol) in CH2Cl2 (0.5 mL), followed by DIPEA (19 μL, 0.107 mmol). After stirring for 5 minutes, the reaction was poured into water (1 mL) and the mixture was extracted with EtOAc (20 mL). The organic extract was washed with H2O, saturated NaHCO3, and brine (5 mL each). The organic layer was then dried over Na2SO4, filtered, and concentrated. The residue was purified by PTLC to afford 4-[3,5-bis(trifluoromethyl)phenyl]-3-{[5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-1,3-oxazolidin-2-one. Rf=0.27 (25% EtOAc/hexanes). LCMS=606.3 (M+1)+. 1H NMR (CD2Cl2, 500 MHz) (Doubling of some peaks observed; atropisomers present in 1:1 ratio) δ 7.84 (s, 1H), 7.19-7.60 (m, 6H), 6.80-6.87 (m, 2H), 3.84-4.68 (m, 5H), 3.68 & 3.64 (2 singlets, 3H), 2.82 (m, 1H), 1.17-1.21 (m, 6H).

Workup

  1. extractionthe mixture was extracted with EtOAc (20 mL)
  2. extractionThe organic extract
  3. washwas washed with H2O, saturated NaHCO3, and brine (5 mL each)
  4. dry with materialThe organic layer was then dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by PTLC

Sources & evidence

ORD record
ord-f31aac12e5e545fe86eba0740c53283a
Source dataset
uspto-grants-2014_05
Patent number
US08735435B2

Reaction notes

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