Hydrochloric Acid → 2-[4-(2-Heptylamino-ethyl)-phenylamino]-2-methyl-propionic acid

HRID 47830Notes

Reaction equation

HRID 47830 reaction equation
B.O1CCCC1.C([O:11][C:12](=[O:34])[C:13]([NH:16][C:17]1[CH:22]=[CH:21][C:20]([CH2:23][CH2:24][NH:25][C:26](=O)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32])=[CH:19][CH:18]=1)([CH3:15])[CH3:14])(C)(C)C.Cl>O1CCCC1>[CH2:26]([NH:25][CH2:24][CH2:23][C:20]1[CH:19]=[CH:18][C:17]([NH:16][C:13]([CH3:14])([CH3:15])[C:12]([OH:34])=[O:11])=[CH:22][CH:21]=1)[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH3:32]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 2723981Borane;tetrahydrofuranHCID 698844682-[4-(2-Heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl ester

Product 1

HCID 234312402-[4-(2-Heptylamino-ethyl)-phenylamino]-2-methyl-propionic acidYield 38%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

1H NMR (400 MHz, CDCl3) δ6.98 (d, 2H), 6.59 (d, 2H), 5.38 (s, 1H), 4.03 (s, 1H), 3.47 (m, 2H), 2.70 (t, 2H), 2.11 (t, 2H), 1.65−1.40 (m, 3H), 1.53 (s, 6H), 1.39 (s, 9H), 1.29 (m, 5H), 0.89 (t, 3H). Borane-tetrahydrofuran complex (1.0M in THF; 6.96 mL, 6.96 mmol) was added to a solution of 2-[4-(2-heptanoylamino-ethyl)-phenylamino]-2-methyl-propionic acid tert-butyl ester (1.36 g, 3.48 mmol) and tetrahydrofuran (25 mL) and the resulting mixture stirred at ambient temperature for 18 h. Additional borane-tetrahydrofuran complex (3.5 mL, 3.5 mmol) was added and the resulting mixture stirred 24 h at ambient temperature before acidifying with 1N aqueous hydrochloric acid. The resulting mixture was then refluxed for 2 h, cooled to ambient temperature and the tetrahydrofuran removed under reduced pressure. The resulting residue was neutralized with saturated aqueous sodium bicarbonate, concentrated under reduced pressure, azeotroped with ethyl acetate and purified by flash column chromatography (10% methanol/1% concentrated ammonium hydroxide/chloroform→15% methanol/1% concentrated ammonium hydroxide/chloroform) to provide 417 mg (38%) of 2-[4-(2-heptylamino-ethyl)-phenylamino]-2-methyl-propionic acid as a white solid.

Workup

  1. additionAdditional borane-tetrahydrofuran complex (3.5 mL, 3.5 mmol) was added
  2. stirringthe resulting mixture stirred 24 h at ambient temperature
  3. temperatureThe resulting mixture was then refluxed for 2 h
  4. temperaturecooled to ambient temperature
  5. customthe tetrahydrofuran removed under reduced pressure
  6. concentrationconcentrated under reduced pressure
  7. customazeotroped with ethyl acetate
  8. custompurified by flash column chromatography (10% methanol/1% concentrated ammonium hydroxide/chloroform→15% methanol/1% concentrated ammonium hydroxide/chloroform)

Sources & evidence

ORD record
ord-7ac79f499ec3473a9b1566bed1d96a50
Source dataset
uspto-grants-2004_03
Patent number
US06699904B2

Reaction notes

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