Diisopropylethylamine → methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)-aminomethylsalicylate

HRID 342834Notes

Reaction equation

HRID 342834 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].[CH:15]([N:18](CC)C(C)C)(C)C.C1(=O)N([O:29][C:30](=O)[CH2:31][CH2:32][CH2:33][CH2:34][CH2:35][NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])C(=O)CC1>CN(C)C=O>[C:40]([O:39][C:37]([NH:36][CH2:35][CH2:34][CH2:33][CH2:32][CH2:31][C:30]([C:5]1[CH:4]=[CH:13][CH:12]=[C:7]([C:8]([O:10][CH3:11])=[O:9])[C:6]=1[O:14][CH2:15][NH2:18])=[O:29])=[O:38])([CH3:43])([CH3:42])[CH3:41]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5074016Boc-6-Ahx-OSuHCID 22556073Methyl 4-aminomethylsalicylate hydrochloride

Product 1

HCID 86752495methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)-aminomethylsalicylateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 4-aminomethylsalicylate hydrochloride (2.25 g, 10.3 mmoles) was suspended in anhydrous N,N-dimethylformamide (30 mL), and N,N-diisopropylethylamine (3.6 mL, 20.7 mmoles) was added, followed by N-tert-butoxycarbonyl-6-aminohexanoic acid succinimidyl ester (3.38 g, 10.3 mmoles). The mixture was stirred under dry nitrogen for 18 hours, during which time all solids dissolved. The solvent was then evaporated to leave a light brown syrup, which was partitioned between ethyl acetate (100 mL) and 1M aqueous hydrochloric acid (100 mL). The layers were separated, and the ethyl acetate solution was washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL). The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered, and evaporated to an amorphous off-white solid. The solid was crystallized form ethyl acetate/hexanes, filtered, and dried in vacuo to afford 3.25 g (80% yield) of methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)-aminomethylsalicylate (m.p. 120°-121° C., open capillary, uncorrected).

Workup

  1. dissolutiondissolved
  2. customThe solvent was then evaporated
  3. customto leave a light brown syrup, which
  4. customwas partitioned between ethyl acetate (100 mL) and 1M aqueous hydrochloric acid (100 mL)
  5. customThe layers were separated
  6. washthe ethyl acetate solution was washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL)
  7. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  8. filtrationfiltered
  9. customevaporated to an amorphous off-white solid
  10. customThe solid was crystallized form ethyl acetate/hexanes
  11. filtrationfiltered
  12. customdried in vacuo

Sources & evidence

ORD record
ord-3d13dff8252a480c9575c3ec44db347e
Source dataset
uspto-grants-1999_01
Patent number
US05859210

Reaction notes

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