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

HRID 1600401Notes

Reaction equation

HRID 1600401 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 toleave a light brown syrup, which was partitioned between ethyl acetate (100mL) 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 crystallizedform 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. customa light brown syrup, which was partitioned between ethyl acetate (100mL) and 1M aqueous hydrochloric acid (100 mL)
  4. customThe layers were separated
  5. washthe ethyl acetate solution was washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL)
  6. dry with materialThe ethyl acetate solution was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. customevaporated to an amorphous off-white solid
  9. filtrationfiltered
  10. customdried in vacuo

Sources & evidence

ORD record
ord-9e6b37e59bf0446bab7e0acd12b7e845
Source dataset
uspto-grants-1998_04
Patent number
US05744627

Reaction notes

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