Triethylamine → methyl N-tert-butoxycarbonylaminomethyl-salicylate

HRID 1600402Notes

Reaction equation

HRID 1600402 reaction equation
Cl.NC[C:4]1[CH:5]=[C:6]([OH:14])[C:7](=[CH:12][CH:13]=1)[C:8]([O:10][CH3:11])=[O:9].[C:15]([O:19][C:20]([O:22]C(OC(C)(C)C)=O)=O)([CH3:18])([CH3:17])[CH3:16].[CH2:30]([N:32](CC)CC)C.C(OCC)(=O)C>CO.O>[C:15]([O:19][C:20]([NH:32][CH2:30][O:14][C:6]1[C:7](=[CH:12][CH:13]=[CH:4][CH:5]=1)[C:8]([O:10][CH3:11])=[O:9])=[O:22])([CH3:18])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 90495Di-tert-butyl dicarbonateHCID 22556073Methyl 4-aminomethylsalicylate hydrochloride

Product 1

HCID 54558375methyl N-tert-butoxycarbonylaminomethyl-salicylateYield 97.4%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

Methyl 4-aminomethylsalicylate hydrochloride (10.9 g, 50 mmoles) was suspended in anhydrous methanol (200 mL) and di-tert-butyldicarbonate (10.9 g, 50 mmoles) and triethylamine (7.0 mL, 50 mmoles) were added. The solid rapidly dissolved with the slow evolution of gas. The reaction mixture was stirred at room temperature for 18 hours under dry nitrogen, then evaporated to dryness to afford a white amorphous mass. This mass waspartitioned between ethyl acetate (200 mL) and water (100 mL). The layers were separated, and the ethyl acetate solution was dried over anhydrous sodium sulfate. The solution was filtered and evaporated to a white solid.This solid was crystallized from ethyl acetate/hexanes, filtered, and driedin vacuo to afford 13.7 g (97% yield) of methyl N-tert-butoxycarbonylaminomethyl-salicylate (m.p. 95°-96° C., open capillary, uncorrected).

Workup

  1. dissolutionThe solid rapidly dissolved with the slow evolution of gas
  2. customevaporated to dryness
  3. customto afford a white amorphous mass
  4. customThe layers were separated
  5. dry with materialthe ethyl acetate solution was dried over anhydrous sodium sulfate
  6. filtrationThe solution was filtered
  7. customevaporated to a white solid.This solid
  8. customwas crystallized from ethyl acetate/hexanes
  9. filtrationfiltered

Sources & evidence

ORD record
ord-92332374744b4c4d8f15829315621546
Source dataset
uspto-grants-1998_04
Patent number
US05744627

Reaction notes

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