4-Bromophenol → (4R)-4-((4-bromophenoxy)methyl)-1,3-oxazolidin-2-one

HRID 2306077Notes

Reaction equation

HRID 2306077 reaction equation
CC1C=CC(S([O:11][CH2:12][C@@H:13]2[CH2:17][O:16][C:15](=[O:18])[NH:14]2)(=O)=O)=CC=1.C(=O)([O-])[O-].[K+].[K+].[Br:25][C:26]1[CH:31]=[CH:30][C:29](O)=[CH:28][CH:27]=1>C(#N)C>[Br:25][C:26]1[CH:31]=[CH:30][C:29]([O:11][CH2:12][C@@H:13]2[CH2:17][O:16][C:15](=[O:18])[NH:14]2)=[CH:28][CH:27]=1

Participants

5

Reactant 3

HCID 78084-BromophenolHCID 11430Potassium Carbonate2×HCID 11032956(S)-(2-oxooxazolidin-4-yl)methyl 4-methylbenzenesulfonate

Product 1

HCID 9835198(4R)-4-((4-bromophenoxy)methyl)-1,3-oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

A solution of Example 1C (4.154 kg), potassium carbonate (2.522 kg), and 4-bromophenol (3.183 kg) in acetonitrile (30.3 kg) was stirred at 70° C. for 23.5 hours, cooled to 55° C., treated with 2% (w/w) K2CO3 (41.52 kg) over 20 minutes, cooled to room temperature, and separated into an aqueous fraction and an organic fraction. The organic fraction was concentrated to approximately one third of its original volume, treated with the aqueous fraction to provide a precipitate, concentrated to remove the remainder of the acetonitrile, treated with the 2% (w/w) K2CO3 solution (41.52 kg), stirred at room temperature for 18 hours, and filtered. The filter cake was rinsed with 2% K2CO3 (16.62 L) air-dried, slurried in ethyl acetate (9.44 kg), and heated at 55° C. This solution was treated with hexanes (23.615 kg) and cooled to room temperature to provide a solid. The solid was filtered, rinsed with a solution of ethyl acetate (2.24 kg) and hexanes (7.3 kg), air dried, and vacuum dried (100 mnu/Hg) at 50° C. with a nitrogen bleed to provide 3.307 kg (79.6%, >99.5% ee) of the desired compound. 1H NMR (300 MHz, DMSO-d6) δ7.91 (br s, 1H), 7.47 (dd, J=17 Hz, 2H), 6.93 (dd, J=17 Hz, 2H), 4.44 (m, 1H), 4.15 (m, 2H), 3.95 (m, 2H).

Workup

  1. temperaturecooled to room temperature
  2. customseparated into an aqueous fraction
  3. concentrationThe organic fraction was concentrated to approximately one third of its original volume
  4. additiontreated with the aqueous fraction
  5. customto provide a precipitate
  6. concentrationconcentrated
  7. customto remove the remainder of the acetonitrile
  8. additiontreated with the 2% (w/w) K2CO3 solution (41.52 kg)
  9. filtrationfiltered
  10. washThe filter cake was rinsed with 2% K2CO3 (16.62 L)
  11. customair-dried
  12. temperatureheated at 55° C
  13. additionThis solution was treated with hexanes (23.615 kg)
  14. temperaturecooled to room temperature
  15. customto provide a solid
  16. filtrationThe solid was filtered
  17. washrinsed with a solution of ethyl acetate (2.24 kg) and hexanes (7.3 kg), air
  18. customdried
  19. customvacuum dried (100 mnu/Hg) at 50° C. with a nitrogen

Sources & evidence

ORD record
ord-75c418c606494e189b1cc0e60930896d
Source dataset
uspto-grants-2002_08
Patent number
US06441189B1

Reaction notes

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