Potassium Carbonate → [2-(4-Oxazol-4-yl-phenoxy)-ethyl]-carbamic acid benzyl ester

HRID 2120152Notes

Reaction equation

HRID 2120152 reaction equation
[O:1]1[CH:5]=[C:4]([C:6]2[CH:11]=[CH:10][C:9]([OH:12])=[CH:8][CH:7]=2)[N:3]=[CH:2]1.[CH2:13]([O:20][C:21]([NH:23][CH2:24][CH2:25]OS(C)(=O)=O)=[O:22])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O>[CH2:13]([O:20][C:21](=[O:22])[NH:23][CH2:24][CH2:25][O:12][C:9]1[CH:8]=[CH:7][C:6]([C:4]2[N:3]=[CH:2][O:1][CH:5]=2)=[CH:11][CH:10]=1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 105883122-(Benzyloxycarbonylamino)ethyl methanesulfonateHCID 124631404-(Oxazol-4-yl)phenol

Product 1

HCID 20620891[2-(4-Oxazol-4-yl-phenoxy)-ethyl]-carbamic acid benzyl esterYield 64%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Conditions

Temperature
85 °C

Procedure

A stirred mixture of 290.0 g (1.80 mol) of 4-oxazol-4-yl-phenol (H. Jones, et al., J. Med. Chem., 21, 1110 (1978)), 737.7 g (2.70 mol) of methanesulfonic acid 2-benzyloxycarbonylamino-ethyl ester, and 746.0 g (5.40 mol) of potassium carbonate in 4.6 l of dry dimethylsulfoxide was heated to about 85° C. An additional 500 ml of dimethylsulfoxide was added and the viscous slurry was stirred at about 80° C. for about an additional two hours. The resulting mixture was cooled to about 50° C., poured into about 1 l of stirred ice water, slurried for about one hour, and then filtered. The wet filter cake was washed with water (2×1 l), and then partially dried by aspiration under vacuum for about two hours. The moist solid was charged into a round-bottomed flask, 6 l of methanol was added, and the mixture was then warmed to about 60° C. where 3 l of water was added. The heating source was removed, the mixture was stirred for about eighteen hours, and then filtered. The filter cake was washed with 2:1 methanol/water (v/v; 2×500 ml), and then dried under vacuum at about 40° C. for about eighteen hours. The title compound (389.5 g, 64% yield) was obtained as a beige powder.

Workup

  1. temperatureThe resulting mixture was cooled to about 50° C.
  2. waitslurried for about one hour
  3. filtrationfiltered
  4. washThe wet filter cake was washed with water (2×1 l)
  5. custompartially dried by aspiration under vacuum for about two hours
  6. additionThe moist solid was charged into a round-bottomed flask
  7. addition6 l of methanol was added
  8. temperaturethe mixture was then warmed to about 60° C. where 3 l of water
  9. additionwas added
  10. customThe heating source was removed
  11. stirringthe mixture was stirred for about eighteen hours
  12. filtrationfiltered
  13. washThe filter cake was washed with 2:1 methanol/water (v/v; 2×500 ml)
  14. customdried under vacuum at about 40° C. for about eighteen hours

Sources & evidence

ORD record
ord-911c20495d3a4f00a9859452810681a5
Source dataset
uspto-grants-2004_02
Patent number
US06689800B2

Reaction notes

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