Hydrochloric Acid → HCID 72558430, compound

HRID 661600Notes

Reaction equation

HRID 661600 reaction equation
C(N(CC)CC)C.Cl.[NH2:9][CH2:10][CH2:11][CH2:12][C:13]([O:15]C)=[O:14].[C:17]([NH:24][C@H:25]([C:27](O)=[O:28])[CH3:26])([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18].Cl.C(N=C=N)C.ON1C2C=CC=CC=2N=N1.[Li+].[OH-].Cl>CN(C)C=O.C(OCC)(=O)C.O1CCCC1.O.CO>[C:20]([O:19][C:17]([NH:24][CH:25]([CH3:26])[C:27]([NH:9][CH2:10][CH2:11][CH2:12][C:13]([OH:15])=[O:14])=[O:28])=[O:18])([CH3:23])([CH3:22])[CH3:21]

Participants

13

Reactant 7

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 85082Tert-butoxycarbonylalanineHCID 27563834-Aminobutyric acid methyl ester hydrochlorideHCID 21883477Ethylcarbodiimide hydrochloride

Product 1

HCID 72558430HCID 72558430, compoundYield 72%

Reagents, catalysts & solvents 5

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of triethylamine (3.1 mL, 1.1 equivalent) and methyl 4-aminobutyrate hydrochloride (3.2 g, 1.05 equivalent) in 25 ml of anhydrous N,N-dimethylformamide was stirred at −10° C. under N2 atmosphere for 10 minutes. Sequential addition of Boc-L-alanine (3.8 g, 1.0 equivalent), N-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (4.2 g, 1.1 equivalents), 1-hydroxybezotriazole (1.8 g, 0.6 equivalent), and 15 mL of anhydrous N,N-dimethylformamide was carried out at the same temperature. The final solution was stirred under N2 atmosphere at room temperature overnight and diluted with ethyl acetate. The resulting solution was washed sequentially with 1 M HCl(aq), saturated NaHCO3(aq), and saturated NaCl(aq), followed by a rapid filtration through a pad of silica gel and Na2SO4. The filtrate was concentrated and dried under reduced pressure to give a crude paste (4.8 g). The paste was stirred in a mixture of 50 mL of tetrahydrofuran, 25 mL of methanol, and 20 mL of water with the presence of LiOH (0.45 g, 1.1 equivalents) for 1 hour at room temperature. The solution was acidified with concentrated HCl and extracted with ethyl acetate. The organic extracts were combined and washed with saturated NaCl(aq) and rapidly filtered through a pad of silica gel and Na2SO4. The filtrate was concentrated and dried under reduced pressure to give 4-(2-t-butoxycarbonylamino-propionylamino)butyric acid as a paste (4.0 g, 72% yield); H1-NMR (DMSO-d6), δ=1.1 ppm (d, 3H), 1.3 ppm (s, 9H), 1.6 ppm (p, 2H), 2.2 ppm (t, 2H), 3.0 ppm (m, 2H), 3.8 ppm (m, 1H), 6.8 ppm (d, 1H), 7.8 ppm (t, 1H).

Workup

  1. washThe resulting solution was washed sequentially with 1 M HCl(aq), saturated NaHCO3(aq), and saturated NaCl(aq)
  2. filtrationfollowed by a rapid filtration through a pad of silica gel and Na2SO4
  3. concentrationThe filtrate was concentrated
  4. customdried under reduced pressure
  5. customto give a crude paste (4.8 g)
  6. extractionextracted with ethyl acetate
  7. washwashed with saturated NaCl(aq)
  8. filtrationrapidly filtered through a pad of silica gel and Na2SO4
  9. concentrationThe filtrate was concentrated
  10. customdried under reduced pressure

Sources & evidence

ORD record
ord-9bdf39ac94ba46aa8ecad1288e9496db
Source dataset
uspto-grants-2011_12
Patent number
US08084643B2

Reaction notes

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