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

HRID 1600397Notes

Reaction equation

HRID 1600397 reaction equation
Cl.NC[C:4]1[CH:5]=[C:6]([OH:15])[C:7](=[CH:13][CH:14]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9].[CH:16]([N:19](CC)C(C)C)(C)C.C1(=O)N(O[C:31](=[O:45])[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][NH:37][C:38]([O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[O:39])C(=O)CC1>CN(C)C=O.C(OCC)(=O)C>[C:41]([O:40][C:38]([NH:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][C:31]([NH:19][CH2:16][O:15][C:6]1[C:7](=[CH:13][CH:14]=[CH:4][CH:5]=1)[C:8]([O:10][CH2:11][CH3:12])=[O:9])=[O:45])=[O:39])([CH3:42])([CH3:43])[CH3:44]

Participants

6

Reactant 3

HCID 81531DiisopropylethylamineHCID 5074016Boc-6-Ahx-OSuHCID 12794728Ethyl 4-aminomethylsalicylate hydrochloride

Product 1

HCID 53930957ethyl (N-tert-butoxycarbonyl-6-aminohexanoyl)aminomethylsalicylateYield 128.1%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethyl 4-aminomethylsalicylate hydrochloride (0.52 g 1.28 mmoles) was suspended in anhydrous N,N-dimethylformamide (25 mL), and N,N-diisopropylethylamine (0.79 mL, 4.53 mmoles) was added, followed by N-tert-butoxycarbonyl-6-aminohexanoic acid succinimidyl ester (0.74 g 2.26mmoles). The mixture was stirred under dry nitrogen for 18 hours, during which time all solids dissolved. The reaction mixture was diluted with ethyl acetate (100 mL) and extracted with 1N aqueous hydrochloric acid (100 mL). The layers were separated, and the ethyl acetate solution was washed with water (100 mL) and saturated aqueous sodium chloride (500 mL).The ethyl acetate solution was dried over anhydrous magnesium sulfate, filtered, and evaporated to afford an amorphous off-white solid. Finally, the solid was crystallized from ethyl acetate, filtered, and dried in vacuo to afford 0.67 g (73% yield) of ethyl (N-tert-butoxycarbonyl-6-aminohexanoyl)aminomethylsalicylate (m.p. 120°-121° C., open capillary, uncorrected).

Workup

  1. dissolutiondissolved
  2. extractionextracted with 1N aqueous hydrochloric acid (100 mL)
  3. customThe layers were separated
  4. washthe ethyl acetate solution was washed with water (100 mL) and saturated aqueous sodium chloride (500 mL).The ethyl acetate solution
  5. dry with materialwas dried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customto afford an amorphous off-white solid
  9. customFinally, the solid was crystallized from ethyl acetate
  10. filtrationfiltered
  11. customdried in vacuo

Sources & evidence

ORD record
ord-244e6e8389484e6f81aac617f757037a
Source dataset
uspto-grants-1998_04
Patent number
US05744627

Reaction notes

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