Acetic Acid → HCID 11577498, compound

HRID 1994589Notes

Reaction equation

HRID 1994589 reaction equation
[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][C:12]=2[CH2:21][N:22]2[C@@H:26]([CH3:27])[C@@H:25]([C:28]3[CH:29]=[C:30]([CH:33]=[CH:34][CH:35]=3)[CH:31]=O)[O:24][C:23]2=[O:36])=[C:4]([O:37][CH3:38])[CH:3]=1.[CH3:39][NH2:40].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].CC(O)=O>ClCCCl.C1COCC1>[F:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[CH:6][C:5]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][C:12]=2[CH2:21][N:22]2[C@@H:26]([CH3:27])[C@@H:25]([C:28]3[CH:35]=[CH:34][CH:33]=[C:30]([CH2:31][NH:40][CH3:39])[CH:29]=3)[O:24][C:23]2=[O:36])=[C:4]([O:37][CH3:38])[CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 5049666Sodium triacetoxyborohydrideHCID 11562778HCID 11562778, compound

Product 1

HCID 11577498HCID 11577498, compound

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-((4S,5R)-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-2-oxo-1,3-oxazolidin-5-yl)benzaldehyde (15 mg, 0.028 mmol) in 1,2-dichloroethane (1 mL) was added methylamine (1 mL of a 2.0 M solution in THF). The resulting mixture was treated with sodium triacetoxyborohydride (34.8 mg, 0.16 mmol) and AcOH (0.05 mL). The mixture was stirred under N2 at room temperature for 5 days. The reaction mixture was quenched with 1N NaOH and the aqueous layer was extracted with ether (3×15 mL). The ether extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (Si) to afford (4S,5R)-3-{[4′-fluoro-5′-isopropyl-2′-methoxy-4-(trifluoromethyl)biphenyl-2-yl]methyl}-4-methyl-5-{3-[(methylamino)methyl]phenyl}-1,3-oxazolidin-2-one. LCMS calc.=545.23; found=545.4 (M+1)+. 1H NMR (500 MHz, CDCl3, 1:1 mixture of atropisomers) δ 7.74 (s, 0.5H); 7.67 (s, 0.5H); 7.64 (s, 0.5H); 7.62 (s, 0.5H); 7.33 (m, 3H); 7.20 (s, 1H); 7.13 (s, 0.5H); 7.12 (s, 0.5H); 7.01 (d, J=8.4 Hz, 0.5H); 6.98 (d, J=8.5 Hz, 0.5H); 6.71 (d, J=2.9 Hz, 0.5H); 6.68 (d, J=2.8 Hz, 0.5H); 5.51 (d, J=8.1 Hz, 0.5H); 5.37 (d, J=8.0 Hz, 0.5H); 4.82 (d, J=15.9 Hz, 0.5H); 4.75 (d, J=15.9 Hz, 0.5H); 4.16 (d, J=15.9 Hz, 0.5H); 3.92 (d, J=15.9 Hz, 0.5H); 3.77 (m, 5.5H); 3.70 (t, J=6.6 Hz, 0.5H); 3.25-3.18 (m, 1H); 2.45 (s, 3H); 1.93 (br, s, 1H); 1.27 (m, 4.5H); 1.19 (d, J=6.9 Hz, 1.5H); 0.53 (d, J=6.5 Hz, 1.5H); 0.40 (d, J=6.5 Hz, 1.5H).

Workup

  1. customThe reaction mixture was quenched with 1N NaOH
  2. extractionthe aqueous layer was extracted with ether (3×15 mL)
  3. washThe ether extracts were washed with brine
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash chromatography (Si)

Sources & evidence

ORD record
ord-f838c85e3d6c495ba6aa25f9cfa322b4
Source dataset
uspto-grants-2010_01
Patent number
US07652049B2

Reaction notes

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