Acetic Acid → tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

HRID 890636Notes

Reaction equation

HRID 890636 reaction equation
[C:1]1([CH2:7][O:8][C:9](=[O:24])[NH:10][C:11]2[CH:16]=[CH:15][C:14]([N:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)=[C:13]([F:23])[CH:12]=2)C=CC=CC=1.O1C[C@@H]1C[NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33].[CH3:37]C(C)([O-])C.[Li+].C(O)(=O)C>C1COCC1.O.C(Cl)Cl>[F:23][C:13]1[CH:12]=[C:11]([N:10]2[CH2:37][C@H:7]([CH2:1][NH:29][C:30](=[O:36])[O:31][C:32]([CH3:35])([CH3:34])[CH3:33])[O:8][C:9]2=[O:24])[CH:16]=[CH:15][C:14]=1[N:17]1[CH2:18][CH2:19][O:20][CH2:21][CH2:22]1

Participants

8

Reactant 4

HCID 176Acetic AcidHCID 5306150Carbamic acid, N-(3-fluoro-4-(4-morpholinyl)phenyl)-, phenylmethyl esterHCID 10080852(S)-N-Boc-2,3-epoxypropylamineHCID 236647642-Propanol, 2-methyl-, lithium salt (1:1)

Product 1

HCID 11418025tert-butyl {(5S)-3-[3-fluoro-4(4-morpholinyl)phenyl]-2-oxo-1,3-oxazolidin-5-yl}methylcarbamate

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a slurry of [3-fluoro-4(4-morpholinyl)phenyl]carbamic acid phenylmethyl ester (Example 1) (1.0039 g, 3.039 mmol) and tert-butyl (2S)oxiranylmethylcarbamate (Example 5) (0.653 g, 3.77 mmol, 1.24 eq) in THF (1.5 ml) at 0° C. was added a solution of lithium t-butoxide in THF (18.07 wt %, 1.735 g, 3.92 mmol, 1.29 eq). After standing 2 days at 20–25° C., methylene chloride (5.0 ml), then acetic acid (0.35 ml, 6.11 mmol, 2.01 eq) followed by water (3.5 ml) was added. The phases were separated and the aqueous washed with methylene chloride (3.5 ml). The combined organics were dried on magnesium sulfate and concentrated to an oil which was shown to contain 1.03 g (85.7%) of Compound III, wherein R1=3-fluoro-4-(4-morpholinyl)phenyl, R3=t-butyl, by external standard HPLC: retention time=4.06 min (column=Zorbax SB-C8 3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes; A=969:30:1 acetonitrile: THF: trifluoroacetic acid; B=949:50:1 water: THF:trifluroracetic acid).

Workup

  1. additionwas added
  2. customThe phases were separated
  3. washthe aqueous washed with methylene chloride (3.5 ml)
  4. customThe combined organics were dried on magnesium sulfate
  5. concentrationconcentrated to an oil which
  6. wash3.5 micron 150×4.6 mm, flow rate=2.0 ml/min, gradient elution from 30:70 A:B to 90:10 A:B over 15 minutes

Sources & evidence

ORD record
ord-85c960d6e7694e318507a98af7a38236
Source dataset
uspto-grants-2006_02
Patent number
US06998420B2

Reaction notes

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