Methyl chloroformate → HCID 178471794, compound

HRID 505311Notes

Reaction equation

HRID 505311 reaction equation
[F:1][C:2]([F:47])([F:46])[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]([O:26][C:27]([F:30])([F:29])[F:28])[CH:23]=[CH:22][C:21]=3[NH:31][CH2:32][C@H:33]3[CH2:38][CH2:37][C@H:36]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:35][CH2:34]3)[C@H:14]2[CH3:45])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl[C:49]([O:51][CH3:52])=[O:50].C(N(C(C)C)CC)(C)C>C(Cl)Cl.CCOC(C)=O>[F:12][C:9]([F:11])([F:10])[C:7]1[CH:6]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([O:26][C:27]([F:29])([F:30])[F:28])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:32][C@H:33]3[CH2:38][CH2:37][C@H:36]([CH2:39][C:40]([O:42][CH2:43][CH3:44])=[O:41])[CH2:35][CH2:34]3)[C:49]([O:51][CH3:52])=[O:50])[C@H:14]2[CH3:45])[CH:4]=[C:3]([C:2]([F:1])([F:46])[F:47])[CH:8]=1

Participants

6

Reactant 3

HCID 6586Methyl chloroformateHCID 81531DiisopropylethylamineHCID 178471773HCID 178471773, compound

Product 1

HCID 178471794HCID 178471794, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of ethyl [trans-4-({[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]amino}methyl)cyclohexyl]acetate (Step A; 50 mg; 0.73 mmol) in CH2Cl2 (3 mL) was added methyl chloroformate (50 μL) followed by diisopropylethylamine (102 μL; 0.585 mmol). The reaction stirred at 40° C. for 24 h. The reaction was diluted with EtOAc (25 mL) and washed successively with sat. NaHCO3, brine, 1N HCl and brine (15 mL each), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) and chiral HPLC (4% IPA/heptane; AD column) to afford ethyl (trans-4-{[[2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl](methoxycarbonyl)amino]methyl}cyclohexyl)acetate as a clear glass. LCMS=743.2 (M+1)+. 1H NMR (CDCl3, 500 MHz): δ 7.90-7.85 (m, 1 H), 7.78 (s, 1 H), 7.75 (s, 1 H), 7.27-7.17 (m, 3 H), 5.71 (d, J=8.0 Hz, 1 H), 5.00-4.54 (m, 1 H), 4.12 (q, J=7.1 Hz, 2 H), 4.10-4.02 (m, 1 H), 3.98-3.82 (m, 2 H), 3.80-3.58 (m, 3 H), 3.14-3.00 (m, 1 H), 2.17 (d, J=6.9 Hz, 2 H), 1.87-1.66 (m, 4 H), 1.52-1.41 (m, 2 H), 1.25 (t, J=7.1 Hz, 3 H), 1.13-0.94 (m, 4 H), 0.69 (d, J=6.4 Hz, 3 H).

Workup

  1. washwashed successively with sat. NaHCO3, brine, 1N HCl and brine (15 mL each)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customThe residue was purified by flash silica gel chromatography (0-25% EtOAc/hexanes gradient) and chiral HPLC (4% IPA/heptane; AD column)

Sources & evidence

ORD record
ord-1afcb552d7344c1cad4b1daff1e95d2f
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

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