1-Hydroxybenzotriazole → HCID 15385777, compound

HRID 1267103Notes

Reaction equation

HRID 1267103 reaction equation
[CH2:1]([S:3]([NH:6][C@@H:7]([C:15]([OH:17])=O)[CH2:8][C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1)(=[O:5])=[O:4])[CH3:2].[NH:18]1[CH2:32][CH2:31][CH2:30][C@H:19]1[C:20]([O:22][CH2:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1)=[O:21].Cl.C1C=CC2N(O)N=NC=2C=1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>C1COCC1>[CH2:1]([S:3]([NH:6][C@@H:7]([C:15]([N:18]1[CH2:32][CH2:31][CH2:30][C@H:19]1[C:20]([O:22][CH2:23][C:24]1[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1)=[O:21])=[O:17])[CH2:8][C:9]1[CH:10]=[CH:11][CH:12]=[CH:13][CH:14]=1)(=[O:4])=[O:5])[CH3:2]

Participants

7

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733413Proline benzyl ester hydrochlorideHCID 15385776N-(Ethylsulfonyl)-D-phenylalanine

Product 1

HCID 15385777HCID 15385777, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirring suspension of EtSO2—D—Phe—OH (257 g, 100 mmol), Pro—OBn.HCl (26.6 g, 110 mmol), HOBT (13.5 g, 100 mmol) and N,N-diisopropylethylamine (43.5 mL, 250 mL) in THF (1 L) at 0° C. was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (23 g, 120 mL). After stirring for 20 h, the solvent was removed in vacuo and the residue was partitioned between ethyl acetate and 1 N citric acid. The organic phase was washed twice with 1 N KHCO3, twice with brine, dried with MgSO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel, eluting with a step gradient of hexanes through 50% ethyl acetate/hexanes. The product containing fractions were combined and concentrated in vacuo to give 29 g (65%) of a clear, thick oil.

Workup

  1. customthe solvent was removed in vacuo
  2. customthe residue was partitioned between ethyl acetate and 1 N citric acid
  3. washThe organic phase was washed twice with 1 N KHCO3, twice with brine
  4. dry with materialdried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed over silica gel
  8. washeluting with a step gradient of hexanes through 50% ethyl acetate/hexanes
  9. additionThe product containing fractions
  10. concentrationconcentrated in vacuo
  11. customto give 29 g (65%) of a clear, thick oil

Sources & evidence

ORD record
ord-435d57a7d35e492e87b9495534fea7c8
Source dataset
uspto-grants-2003_04
Patent number
US06552038B1

Reaction notes

Loading…