4-(((Tert-butoxy)carbonyl)amino)butanoic acid → {3-[3-(3-Ethylcarbamoyl-propylcarbamoyl)-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester

HRID 1726447Notes

Reaction equation

HRID 1726447 reaction equation
C(OC(=O)[NH:7][CH2:8][CH2:9][CH2:10][C:11](=[O:21])[NH:12][CH2:13][CH2:14][CH2:15][C:16](=[O:20])[NH:17][CH2:18][CH3:19])(C)(C)C.[C:23]([NH:30][CH2:31][CH2:32][CH2:33][C:34]([OH:36])=O)([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]>CO.Cl>[C:26]([O:25][C:23](=[O:24])[NH:30][CH2:31][CH2:32][CH2:33][C:34](=[O:36])[NH:7][CH2:8][CH2:9][CH2:10][C:11](=[O:21])[NH:12][CH2:13][CH2:14][CH2:15][C:16](=[O:20])[NH:17][CH2:18][CH3:19])([CH3:27])([CH3:28])[CH3:29]

Participants

5

Reactant 2

HCID 2948944-(((Tert-butoxy)carbonyl)amino)butanoic acidHCID 86588667HCID 86588667, compound

Product 1

HCID 86597545{3-[3-(3-Ethylcarbamoyl-propylcarbamoyl)-propylcarbamoyl]-propyl}-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolvent

Procedure

Boc-Protected derivative 4 (22.3 g, 70.7 mmol) was stirred in a mixture of MeOH (200 ml) and HCl (12%, 81 ml) for 48 h, concentrated to dryness in vacuo, dissolved in H2O, and washed 3 times with CHCl3. Water was removed on a rotary evaporator at 45° C. The resulting hydrochloride was dissolved in a mixture of CH2Cl2 (600 ml) and aq. Na2CO3 (20%, 100 ml), cooled on an ice bath, and Bt-derivative 2 (22.47 g, 70.15 mmol) was added. The cooling bath was removed and the mixture was stirred for 18 h with a mechanical stirrer. The main part of the CH2Cl2 was removed on a rotary evaporator, the reaction mixture was suspended in water and filtered. The product was triturated in EtOAc, filtered, washed with petr. ether and dried in vacuo. Yield 25.46 g (90%). mp: 170-171° C. 1H NMR (CDCl3/CD3OD): 1.14 (t, J=7.30, 3H), 1.44 (s, 9H), 1.72-1.85 (m, 6H), 2.10-2.23 (m, 6H), 3.06-3.12 (m, 2H), 3.18-3.26 (m, 6H), 5.57 (bs, 1H), 7.32 (bs, 1H), 7.46 (bs, 1H), 7.60 (bs, 1H). 13C NMR (CDCl3/CD3OD): 14.22, 24.73, 25.32, 25.39, 25.96, 28.15, 33.33, 33.59, 34.12, 34.25, 38.60, 39.64, 79.29, 156.68, 173.39, 173.88. ESI-MS: 423.4 (MNa+), 401.4 (MH+).

Workup

  1. concentrationconcentrated to dryness in vacuo
  2. dissolutiondissolved in H2O
  3. washwashed 3 times with CHCl3
  4. customWater was removed on a rotary evaporator at 45° C
  5. dissolutionThe resulting hydrochloride was dissolved in a mixture of CH2Cl2 (600 ml) and aq. Na2CO3 (20%, 100 ml)
  6. temperaturecooled on an ice bath
  7. customThe cooling bath was removed
  8. customThe main part of the CH2Cl2 was removed on a rotary evaporator
  9. filtrationfiltered
  10. customThe product was triturated in EtOAc
  11. filtrationfiltered
  12. washwashed with petr
  13. dry with materialether and dried in vacuo

Sources & evidence

ORD record
ord-ddeed0a847204910b6aec2d0c9dbd0ce
Source dataset
uspto-grants-2009_02
Patent number
US07491849B2

Reaction notes

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