Diisopropylethylamine → 4-{[(2-tert-Butoxycarbonylethyl)-(15-tert-butoxycarbonyl-pentadecanoyl)amino]methyl}benzoic acid

HRID 444977Notes

Reaction equation

HRID 444977 reaction equation
[C:1]([O:5][C:6](=[O:24])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][C:21]([OH:23])=O)([CH3:4])([CH3:3])[CH3:2].ON1C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[C:44]([O:48][C:49]([CH2:51][CH2:52][NH:53][CH2:54][C:55]1[CH:63]=[CH:62][C:58]([C:59]([OH:61])=[O:60])=[CH:57][CH:56]=1)=[O:50])([CH3:47])([CH3:46])[CH3:45]>C(OCC)(=O)C>[C:44]([O:48][C:49]([CH2:51][CH2:52][N:53]([CH2:54][C:55]1[CH:63]=[CH:62][C:58]([C:59]([OH:61])=[O:60])=[CH:57][CH:56]=1)[C:21](=[O:23])[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][CH2:9][CH2:8][CH2:7][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:24])=[O:50])([CH3:47])([CH3:45])[CH3:46]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 5781772316-(Tert-butoxy)-16-oxohexadecanoic acidHCID 596879094-[(2-tert-Butoxycarbonylethylamino)methyl]benzoic acid

Product 1

HCID 580794854-{[(2-tert-Butoxycarbonylethyl)-(15-tert-butoxycarbonyl-pentadecanoyl)amino]methyl}benzoic acidYield 27.3%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

Hexadecanedioic acid mono-tert-butyl ester (0.3 g, 0.88 mmol) was dissolved in ethyl acetate. N-Ethyl-N-(3-dimethylaminopropyl)-carbodiimide hydrochloride (0.167 g, 0.88 mmol) and 1-hydroxy-7-azabenzotriazole (0.119 g, 0.88 mmol) was added and the mixture was stirred at 50° C. for 1 hour. After cooling to room temperature, diisopropylethylamin (0.45 mL, 2.63 mmol) was added followed by 4-[(2-tert-Butoxycarbonylethylamino)methyl]benzoic acid (0.489 g, 1.75 mmol). The mixture was stirred overnight under nitrogen at room temperature. The mixture was separated between ethyl acetate (100 mL) and water (2×50 mL). The organic phase was dried (Na2SO4), solvent removed in vacuo. The crude product was purified by RP-HPLC on C18-column, buffer A: 0.1% TFA, buffer B: MeCN+0.1% TFA; gradient 80-100% B to yield the title compound (145 mg, 27%).

Workup

  1. temperatureAfter cooling to room temperature
  2. stirringThe mixture was stirred overnight under nitrogen at room temperature
  3. customThe mixture was separated between ethyl acetate (100 mL) and water (2×50 mL)
  4. dry with materialThe organic phase was dried (Na2SO4), solvent
  5. customremoved in vacuo
  6. customThe crude product was purified by RP-HPLC on C18-column, buffer A: 0.1% TFA, buffer B

Sources & evidence

ORD record
ord-444d228316bc40eda640ce600f79ecff
Source dataset
uspto-grants-2013_07
Patent number
US08476228B2

Reaction notes

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