Methyl chloroformate → HCID 24896269, compound

HRID 505290Notes

Reaction equation

HRID 505290 reaction equation
[F:1][C:2]([F:38])([F:37])[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][CH:33]([CH3:35])[CH3:34])[C@H:14]2[CH3:36])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.Cl[C:40]([O:42][CH3:43])=[O:41].C(N(C(C)C)C(C)C)C>C(Cl)Cl.CCOC(C)=O>[F:38][C:2]([F:1])([F:37])[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:28])([F:29])[F:30])[CH:23]=[CH:22][C:21]=3[N:31]([CH2:32][CH:33]([CH3:34])[CH3:35])[C:40](=[O:41])[O:42][CH3:43])[C@H:14]2[CH3:36])[CH:6]=[C:7]([C:9]([F:11])([F:10])[F:12])[CH:8]=1

Participants

6

Reactant 3

HCID 6586Methyl chloroformate2×HCID 81531Diisopropylethylamine2×HCID 24896195HCID 24896195, compound

Product 1

HCID 24896269HCID 24896269, compound

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-3-[2-(isobutylamino)-5-(trifluoromethoxy)benzyl]-4-methyl-1,3-oxazolidin-2-one (25.6 mg, 0.0502 mmol) in CH2Cl2 (0.5 mL) was added methyl chloroformate (7.7 μL, 0.100 mmol), followed by EtN(i—Pr)2 (70 μL, 0.402 mmol) The reaction was stirred at room temperature for 24 hours, and then methyl chloroformate (7.7 μL, 0.100) and EtN(i—Pr)2 (70 μL, 0.402 mmol) were added. The reaction was stirred for 96 hours and then diluted with EtOAc (20 mL), and washed with saturated NaHCO3 solution, brine, and 1 N HCl (10 mL each). The organic layer was dried over Na2SO4, filtered, and concentrated. Purification of the residue by PTLC (25% EtOAc/hexanes) afforded methyl [2-({(4S,5R)-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-2-oxo-1,3-oxazolidin-3-yl}methyl)-4-(trifluoromethoxy)phenyl]isobutylcarbamate. Rf=0.29 (25% EtOAc/hexanes). LCMS=617.3 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.89-7.87 (m, 1H), 7.78-7.76 (m, 2H), 7.24-7.17 (m, 3H), 5.73-5.71 (m, 1H), 5.01-4.75 (m, 2H), 4.07-3.06 (m, 3H), 1.83-1.75 (m, 1H), 1.27-1.21 (m, 3H), 0.99-0.91 (m, 6H), 0.70-0.68 (m, 3H).

Workup

  1. stirringThe reaction was stirred for 96 hours
  2. washwashed with saturated NaHCO3 solution, brine, and 1 N HCl (10 mL each)
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification of the residue by PTLC (25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-a024a238352b49bf9ffcf40d3a26b1b3
Source dataset
uspto-grants-2010_08
Patent number
US07781426B2

Reaction notes

Loading…