Diisopropylethylamine → methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)aminomethyl-2,6-dihydroxybenzoate

HRID 363160Notes

Reaction equation

HRID 363160 reaction equation
Cl.NC[C:4]1[CH:13]=[C:12]([OH:14])[C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([OH:15])[CH:5]=1.[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:41]([O:40][C:38]([NH:37][CH2:36][CH2:35][CH2:34][CH2:33][CH2:32][C:31]([NH:19][CH2:16][C:13]1[C:12]([OH:14])=[C:7]([C:6]([OH:15])=[CH:5][CH:4]=1)[C:8]([O:10][CH3:11])=[O:9])=[O:45])=[O:39])([CH3:42])([CH3:43])[CH3:44]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 5074016Boc-6-Ahx-OSuHCID 22556072Methyl 4-aminomethyl-2,6-dihydroxybenzoate hydrochloride

Product 1

HCID 86753339methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)aminomethyl-2,6-dihydroxybenzoateYield 80%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 4-aminomethyl-2,6-dihydroxybenzoate hydrochloride (1.50 grams, 6.4 mmoles) was suspended in anhydrous N,N-dimethylformamide (25 mL), and N,N-diisopropylethylamine (2.2 mL, 12.8 mmoles) was added, followed by N-tert-butoxycarbonyl-6-aminohexanoic acid succinimidyl ester (2.10 grams, 6.4 mmoles). The mixture was stirred under dry nitrogen for 4 hours, during which time all solids dissolved. The solvent was then evaporated to leave a light brown syrup, which was partitioned between ethyl acetate (70 mL) and 1M aqueous hydrochloric acid (50 mL). The layers were separated, and the ethyl acetate solution was washed with saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 mL). The ethyl acetate solution was dried over anhydrous sodium sulfate, filtered, and evaporated to an amorphous off-white solid. The solid was crystallized from ethyl acetate/hexanes, filtered, and dried in vacuo to afford 2.10 grams (80% yield) of methyl (N-tert-butoxycarbonyl-6-aminohexanoyl)aminomethyl-2,6-dihydroxybenzoate (m.p. 73°-76° 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 (70 mL) and 1M aqueous hydrochloric acid (50 mL)
  5. customThe layers were separated
  6. washthe ethyl acetate solution was washed with saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 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 from ethyl acetate/hexanes
  11. filtrationfiltered
  12. customdried in vacuo

Sources & evidence

ORD record
ord-7bcd067e2f6348afa7de969599485b38
Source dataset
uspto-grants-1999_02
Patent number
US05872224

Reaction notes

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