Ammonium Chloride → HCID 59268009, compound

HRID 1809398Notes

Reaction equation

HRID 1809398 reaction equation
[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[NH:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.[O:19]1[CH2:24][CH2:23][CH2:22][CH2:21][CH:20]1[C:25](Cl)=[O:26].[NH4+].[Cl-]>C1COCC1>[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:25]([C@@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][O:19]1)=[O:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1.[CH2:1]([C@H:8]1[CH2:12][O:11][C:10](=[O:13])[N:9]1[C:25]([C@H:20]1[CH2:21][CH2:22][CH2:23][CH2:24][O:19]1)=[O:26])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 25517Ammonium ChlorideHCID 736225(S)-4-Benzyl-2-oxazolidinoneHCID 15731743TETRAHYDROPYRAN-2-CARBONYL CHLORIDEHCID 178418339Butyllithium

Product 2

HCID 59267855HCID 59267855, compoundYield 11%HCID 59268009HCID 59268009, compoundYield 22%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-70 °C

Procedure

To a stirred solution of (4S)-4-benzyl-1,3-oxazolidin-2-one (9.31 g, 52.56 mmol) in anhydrous THF (150 mL) is added n-butyllithium (2.5 M in hexanes, 21.05 mL, 52.56 mmol) over 25 min at −78° C. Then a solution of tetrahydro-pyran-2-carbonyl chloride (7.1 g, 47.78 mmol) in anhydrous THF (12 mL) is added dropwise. The reaction is stirred at −70° C. for 0.5 h, then allowed to warm to room temperature and stirred for 2 h. Saturated aqueous NH4Cl solution (20 mL) is added and the reaction mixture is concentrated under reduced pressure. The residue is partitioned between ethyl acetate (200 mL) and water (50 mL). The organic layer is separated, washed with saturated aqueous NaHCO3 solution (2×50 mL), brine (50 mL), dried (MgSO4) and filtered. The filtrate is concentrated under reduced pressure and the mixture of diastereoisomers is separated by multiple column chromatography (silica, eluent: toluene, 0-20% TBME) to afford 3.81 g of (4S)-4-benzyl-3-{[(2S)-oxan-2-yl]carbonyl}-1,3-oxazolidin-2-one (78%, yield: 22%; ES-MS: m/z 290 [M+H]; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.46-1.72 (4H, m), 1.81-1.90 (2H, m), 2.71 (1H, dd, J=13.43, 9.77 Hz), 3.30 (1H, dd, J=13.43, 3.05 Hz), 3.54 (1H, td, J=11.52, 2.14 Hz), 4.06-4.19 (3H, m), 4.60 (1H, m, J=9.88, 6.75, 3.28, 3.28 Hz), 4.97 (1H, dd, J=10.60, 1.91 Hz), 7.12-7.30 (5H, m)) and 1.65 g of (4S)-4-benzyl-3-{[(2R)-oxan-2-yl]carbonyl}-1,3-oxazolidin-2-one (93%, yield: 11%; ES-MS: m/z 290 [M+H]; 1H NMR (500 MHz, CHLOROFORM-d) δ ppm 1.54-1.80 (4H, m), 1.90-2.06 (2H, m), 2.83 (1H, dd, J=13.58, 9.16 Hz), 3.24 (1H, dd, J=13.50, 3.28 Hz), 3.53-3.61 (1H, m), 4.11-4.17 (1H, m), 4.19-4.24 (1H, m), 4.25-4.31 (1H, m), 4.71-4.78 (1H, m), 4.96 (1H, dd, J=10.60, 2.06 Hz), 7.16-7.37 (5H, m))

Workup

  1. temperatureto warm to room temperature
  2. stirringstirred for 2 h
  3. concentrationthe reaction mixture is concentrated under reduced pressure
  4. customThe residue is partitioned between ethyl acetate (200 mL) and water (50 mL)
  5. customThe organic layer is separated
  6. washwashed with saturated aqueous NaHCO3 solution (2×50 mL), brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationThe filtrate is concentrated under reduced pressure
  10. additionthe mixture of diastereoisomers
  11. customis separated by multiple column chromatography (silica, eluent: toluene, 0-20% TBME)

Sources & evidence

ORD record
ord-548a9804c8fd4f41a92852dd61c60b98
Source dataset
uspto-grants-2013_01
Patent number
US08362039B2

Reaction notes

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