Oxalyl chloride → HCID 18660380, compound

HRID 962480Notes

Reaction equation

HRID 962480 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C:11]([CH2:20][O:21][CH:22]([C:26]2[CH:31]=[C:30]([C:32]([F:35])([F:34])[F:33])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[C:23]([OH:25])=O)([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(Cl)(=O)C(Cl)=O.[Li]CCCC.[CH2:51]([C@@H:58]1[CH2:62][O:61][C:60](=[O:63])[NH:59]1)[C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=1>ClCCl.O1CCCC1.CN(C)C=O>[C:1]([O:5][C:6]([N:8]1[CH2:9][CH2:10][C:11]([CH2:20][O:21][CH:22]([C:26]2[CH:31]=[C:30]([C:32]([F:33])([F:35])[F:34])[CH:29]=[C:28]([C:36]([F:39])([F:38])[F:37])[CH:27]=2)[C:23]([N:59]2[C@H:58]([CH2:51][C:52]3[CH:57]=[CH:56][CH:55]=[CH:54][CH:53]=3)[CH2:62][O:61][C:60]2=[O:63])=[O:25])([C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:12][CH2:13]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]

Participants

8

Reactant 4

HCID 65578Oxalyl chlorideHCID 2734969(R)-4-Benzyl-2-oxazolidinoneHCID 10745467HCID 10745467, compoundHCID 178418339Butyllithium

Product 1

HCID 18660380HCID 18660380, compound

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

The compound of step (a) above (1.0 g, 1.7 mmol) was dissolved in anhydrous dichloromethane (50 ml). Dimethylformamide(0.05 ml) was added followed by oxalyl chloride (0.2 ml, 2.3 mmol) dropwise. After stirring at 25° C. for 0.5 hours the solvent was removed in vacuo. The resulting residue was azeotroped with toluene (2×50 ml) then, as a solution in anhydrous toluene (5 ml), added at -78° C. to the lithium anion of (4R)-4-benzyl-2-oxazolidinone (generated by adding n-BuLi (1.1 ml, 1.6M, 1.7 mmol) to a solution of (4R)-(+)-4-benzyl-2-oxazolidinone (0.301 g, 1.7 mmol) in tetrahydrofuran (5 ml) at -78° C.). The resulting colorless solution was stirred at -78° C. for a further 0.75 hours and quenched by addition of saturated ammonium chloride solution (30 ml). The product was extracted into ethyl acetate (2×30 ml) then the organic layer was dried over MgSO4 and filtered. The clear oil obtained after removal of solvent in vacuo was purified by chromatography on silica gel eluting first with 20% ethyl acetate/hexane to obtain the title compound, diastereomer A (0.350 g), and then with 30% ethyl acetate/hexane to obtain the title compound, diastereomer B (0.380 g). Diastereomer A was converted to a mixture (1:2) of diastereomer A and diastereomer B by treating a solution in dichloromethane with anhydrous triethylamine for 16 hours. The solvents were evaporated and the mixture separated by chromatography as described above to obtain diastereomer B: 1H NMR (250 MHz, CDCl3) δ 7.78 (s, 1H), 7.70 (s, 2H), 7.10-7.30 (m, 8H), 6.88 (m, 2H), 5.86 (s, 1H), 4.62 (m, 1H), 4.06-4.12 (m, 2H), 3.68 (m, 2H), 3.54 (d, J=7 Hz, 1 H), 3.22 (d, J=7 Hz, 1 H), 2.96 (m, 3H), 2.54 (dd, J=7, 2 Hz, 1H), 2.1 (m, 2H), 1.8 (m, 2H), 1.34 (s, 9H).

Workup

  1. customwas removed in vacuo
  2. customThe resulting residue was azeotroped with toluene (2×50 ml)
  3. additionas a solution in anhydrous toluene (5 ml), added at -78° C. to the lithium anion of (4R)-4-benzyl-2-oxazolidinone (
  4. stirringThe resulting colorless solution was stirred at -78° C. for a further 0.75 hours
  5. customquenched by addition of saturated ammonium chloride solution (30 ml)
  6. extractionThe product was extracted into ethyl acetate (2×30 ml)
  7. dry with materialthe organic layer was dried over MgSO4
  8. filtrationfiltered
  9. customThe clear oil obtained
  10. customafter removal of solvent in vacuo
  11. customwas purified by chromatography on silica gel eluting first with 20% ethyl acetate/hexane

Sources & evidence

ORD record
ord-021ec8f30b2e487ca7b60d64032c082d
Source dataset
uspto-grants-1998_06
Patent number
US05760018

Reaction notes

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