Water → HCID 14819188, compound

HRID 2352398Notes

Reaction equation

HRID 2352398 reaction equation
[C:1]([O:5][C:6](=[O:28])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:27])[C@H:13]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[NH2:14])([CH3:4])([CH3:3])[CH3:2].Br[CH:30]1[CH2:35][CH:34]([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[O:33][C:31]1=[O:32].C(N(CC)CC)C.O>C(#N)C>[C:1]([O:5][C:6](=[O:28])[C@@H:7]1[CH2:11][CH2:10][CH2:9][N:8]1[C:12](=[O:27])[C@H:13]([CH2:15][CH2:16][CH2:17][CH2:18][NH:19][C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[NH:14][CH:30]1[CH2:35][CH:34]([CH2:36][CH2:37][CH2:38][CH2:39][CH3:40])[O:33][C:31]1=[O:32])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 14010669H-Lys(Boc)-Pro-OtBuHCID 19844298HCID 19844298, compound

Product 1

HCID 14819188HCID 14819188, compoundYield 72.2%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
70 °C

Procedure

Dissolved in 50 ml of acetonitrile were 2.00 g of Nε -t-butoxycarbonyl-L-lysyl-L-proline t-butyl ester and 3.53 g of 2-bromo-4-pentyl-γ-butyrolactone. After a dropwise addition of 0.76 g of triethylamine, the resultant mixture was heated and stirred at 70° C. for 40 hours. The reaction mixture was poured into chilled water, followed by extraction with ethyl acetate. The extract was washed successively with water, a 2% aqueous solution of sodium hydrogencarbonate, and water. After drying the extract over anhydrous sodium sulfate, it was distilled under reduced pressure. The residue was isolated and purified by chromatography on a silica gel column (chloroform:ethyl acetate=10:1-5:1), thereby obtaining as a colorless syrupy substance 2.00 g of Nα -(2-oxo-5-pentyl-3-tetrahydrofuranyl)-Nε -t-butoxycarbonyl-L-lysyl-L-proline t-butyl ester [in the formula (I), R1 =--(CH2)4CH3, R2 =H, R3 =--(CH2)4NHCOO-t-Bu, R4 and R5 =--(CH2)3 --, R6 = t-Bu (Compound 27)]. Upon analysis of Compound 27 by high-performance liquid chromatography, it was found to be a mixture of 4 types of diastereomers.

Workup

  1. additionThe reaction mixture was poured
  2. extractionfollowed by extraction with ethyl acetate
  3. washThe extract was washed successively with water
  4. customAfter drying the
  5. extractionextract over anhydrous sodium sulfate, it
  6. distillationwas distilled under reduced pressure
  7. customThe residue was isolated
  8. custompurified by chromatography on a silica gel column (chloroform:ethyl acetate=10:1-5:1)

Sources & evidence

ORD record
ord-353cce45bf644e08aee2593a27521fe7
Source dataset
uspto-grants-1989_10
Patent number
US04876359

Reaction notes

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