Ammonium Chloride → 3-(S)-(4-(S)-Isopropyl-2-oxo-oxazolidine-3-carbonyl)-octanoic acid tert-butyl ester

HRID 431546Notes

Reaction equation

HRID 431546 reaction equation
[C:1]([N:9]1[C@@H:13]([CH:14]([CH3:16])[CH3:15])[CH2:12][O:11][C:10]1=[O:17])(=[O:8])[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][CH3:7].[Li+].C[Si]([N-][Si](C)(C)C)(C)C.[C:28]([O:32][C:33](=[O:36])[CH2:34]Br)([CH3:31])([CH3:30])[CH3:29].[NH4+].[Cl-]>C1COCC1>[C:28]([O:32][C:33](=[O:36])[CH2:34][C@@H:2]([C:1]([N:9]1[C@@H:13]([CH:14]([CH3:16])[CH3:15])[CH2:12][O:11][C:10]1=[O:17])=[O:8])[CH2:3][CH2:4][CH2:5][CH2:6][CH3:7])([CH3:31])([CH3:30])[CH3:29]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 79177tert-Butyl bromoacetateHCID 2733832Lithium HexamethyldisilazideHCID 108576323-Heptanoyl-4-(S)-isopropyl-oxazolidin-2-one

Product 1

HCID 100211153-(S)-(4-(S)-Isopropyl-2-oxo-oxazolidine-3-carbonyl)-octanoic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of 4(37.082 g, 0.154 mol) in THF (300 mL) at −78° C. is added LiHMDS in THF (1.0 M, 0.162 mol, 162 mL) via cannula. The solution is stirred at −78° C. for 1 h. tert-Butylbromoacetate is added and then stirred for 30 more minutes. It is then gradually warmed to 0° C. and stirred at this temperature for 30 min. To this solution is gradually added 100 mL saturated aqueous solution of NH4Cl. The bulk of the THF is removed by rotary evaporation and the remaining mixture was extracted with CH2Cl2 (100 mL×3). The combined CH2Cl2 extracts is washed consecutively with 1N NaOH, 1 N HCl, saturated NaHCO3, and brine. It is then dried over MgSO4 and concentrated in vacuo. The residue is chromatographed in silica gel using hexane/ethyl acetate (5:1) as eluant to afford 5. 1H NMR (400 MHz, CDCl3) δ0.85 (t, J=6.8 Hz, 3 H), 0.91 (d, J=8.15 Hz, 3 H), 0.93 (d, J=8.15 Hz, 3 H), 1.18-1.35 (m, 6 H), 1.40 (s, 9 H), 1.35-1.49 (m, 1 H), 1.56-1.66 (m, 1 H), 2.31-2.39 (m, 1 H), 2.44 (dd, J=16.6, 4.5, 1 H), 2.73 (dd, J=16.6, 10.3, 1 H), 4.11-4.20 (m, 1 H), 4.44 (m, 1 H); 13C NMR (75.45 MHz, CDCl3) δ13.9, 14.4, 17.9, 22.4, 26.4, 27.9, 28.0, 31.4, 31.6, 31.7, 37.0, 39.2, 58.6, 62.9, 80.3, 153.5, 171.2, 175.8. HRMS calcd for C19H34NO5 (MH+): 356.2436. Found (DCI): 356.2418 (Δ=5.3 ppm).

Workup

  1. additionis added
  2. stirringstirred at this temperature for 30 min
  3. customThe bulk of the THF is removed by rotary evaporation
  4. extractionthe remaining mixture was extracted with CH2Cl2 (100 mL×3)
  5. washThe combined CH2Cl2 extracts is washed consecutively with 1N NaOH, 1 N HCl, saturated NaHCO3, and brine
  6. dry with materialIt is then dried over MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe residue is chromatographed in silica gel
  9. customto afford 5

Sources & evidence

ORD record
ord-11d4f6294cd44c3f98e9cc9b7eaf40d7
Source dataset
uspto-grants-2003_12
Patent number
US06660741B2

Reaction notes

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