Hydrochloric Acid → [(5r)-3-(4-Bromo-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl 3-nitrobenzene sulfonate

HRID 2120075Notes

Reaction equation

HRID 2120075 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[CH2:12][C@H:11]([CH2:13][OH:14])[O:10][C:9]2=[O:15])=[CH:4][C:3]=1[F:16].C(N(CC)CC)C.[N+:24]([C:27]1[CH:28]=[C:29]([S:33](Cl)(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1)([O-:26])=[O:25].Cl>C(Cl)Cl.CO>[N+:24]([C:27]1[CH:28]=[C:29]([S:33]([O:14][CH2:13][C@@H:11]2[O:10][C:9](=[O:15])[N:8]([C:5]3[CH:6]=[CH:7][C:2]([Br:1])=[C:3]([F:16])[CH:4]=3)[CH2:12]2)(=[O:35])=[O:34])[CH:30]=[CH:31][CH:32]=1)([O-:26])=[O:25]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 84763-Nitrobenzenesulfonyl chloride2×HCID 341779043-(4-Bromo-3-fluorophenyl)-5-(hydroxymethyl)oxazolidin-2-one, (R)-

Product 1

HCID 20619475[(5r)-3-(4-Bromo-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl 3-nitrobenzene sulfonateYield 95.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

To a slurry of 907 g (3.13 mol) of (5R)-3-(4-bromo-3-fluorophenyl)-5-(hydroxymethyl)-1,3-oxazolidin-2-one in 4.5 L of CH2Cl2 in a 22 L round bottom flask was added 654 mL (4.69 mol, 1.50 equiv.) of triethylamine. The mixture was cooled to 0° C., and a solution of 832 g (34.75 mol, 1.20 equiv) of m-nitrobenzenesulfonyl chloride in 2 L of CH2Cl2 was added, keeping the temperature below 6° C. The mixture was sampled for HPLC, and an additional 55 g of solid m-nitrobenzenesulfonyl chloride was added to drive the reaction to completion. Hydrochloric acid (1M, 4.5 L) was added to the slurry. The solids were collected by filtration and washed with water. The phases in the filtrate were separated, and the aqueous later was extracted with 2×500 mL of CH2Cl2. The combined organic layers were concentrated and combined with the solids previously isolated, 2 L of CH2Cl2 and 2 L of methanol. This slurry was distilled on a rotary evaporator, keeping the volume at ˜5 L by adding methanol. The solids were collected by filtration, washed with 1 L of MeOH, and air dried to afford 1415 g (95%) of [(5R)-3-(4-bromo-3-fluorophenyl)-2-oxo-1,3-oxazolidin-5-yl]methyl 3-nitrobenzene sulfonate: TLC Rf=0.15 (50% EtOAc.hexanes); HPLC rt=5.68 min; mp 153-156°; [α]D=−76.6° C.=1, MeOH/CH2Cl2), 1H NMR (DMSO) δ8.77 (d, 1H, J=8.2 Hz), 8.71 (s,1H), 8.52 (d, 1H, 7.9 Hz), 8.14 (t, 1H, J=8.1 Hz), 7.85 (t, 1H, J=8.5 Hz), 7.73 (dd, 1H, J=2.3, 11.4 Hz), 7.40 (d, 1H, J=8.9 Hz), 5.12 (m, 1H), 4.68 (m, 2H), 4.28 (t, 1H, J=9.4 Hz), 3,89 (m, 1H); 13C NMR (DMSO) δ157.3 (s, JCF=242 hz), 152.4 (S), 147.2 (S), 138.3 (S, JCF=10 hz), 135.4 (S), 132.7 (D), 132.6 (D), 131.1 (D), 128.2 (D), 121.7 (D), 114.2 (D), 105.3 (D, JCF=29 Hz), 100.6 (s, JCF=20 Hz), 70.4 (t), 69.0 (d), 44.8 (t); Anal. calc'd for C16H12BrFN2O7S: C, 40.44; H, 2.55; N, 5.89; Br, 16.81; found: C. 40.22; H, 2.45; N, 5.86; Br, 16.60.

Workup

  1. customthe temperature below 6° C
  2. aliquotThe mixture was sampled for HPLC
  3. customthe reaction to completion
  4. filtrationThe solids were collected by filtration
  5. washwashed with water
  6. customThe phases in the filtrate were separated
  7. extractionthe aqueous later was extracted with 2×500 mL of CH2Cl2
  8. concentrationThe combined organic layers were concentrated
  9. custompreviously isolated
  10. distillationThis slurry was distilled on a rotary evaporator
  11. additionby adding methanol
  12. filtrationThe solids were collected by filtration
  13. washwashed with 1 L of MeOH, and air
  14. customdried

Sources & evidence

ORD record
ord-068365e8dec14b5fa7e1732566baf4d7
Source dataset
uspto-grants-2004_02
Patent number
US06689769B2

Reaction notes

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