Hydrochloric Acid → HCID 131717236, compound

HRID 2373075Notes

Reaction equation

HRID 2373075 reaction equation
[NH:1]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[C@H:2]([C:10]([NH:12][CH2:13][C:14]([NH:16][C@H:17]([C:22]([OH:24])=O)[CH2:18][CH:19]([CH3:21])[CH3:20])=[O:15])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.CN1CCOCC1.Cl.[NH2:40][C@H:41]([C:46]([CH2:48][F:49])=[O:47])[CH2:42][CH:43]([CH3:45])[CH3:44]>C1COCC1.CN(C=O)C>[NH:1]([C:25]([O:27][C:28]([CH3:29])([CH3:31])[CH3:30])=[O:26])[C@H:2]([C:10]([NH:12][CH2:13][C:14]([NH:16][C@H:17]([C:22]([NH:40][C@H:41]([C:46]([CH2:48][F:49])=[O:47])[CH2:42][CH:43]([CH3:45])[CH3:44])=[O:24])[CH2:18][CH:19]([CH3:21])[CH3:20])=[O:15])=[O:11])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 79724-Methylmorpholine2×HCID 131716517HCID 131716517, compoundHCID 131717235HCID 131717235, compound

Product 1

HCID 131717236HCID 131717236, compound

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of Boc-LeuCH2F (1.53 g, 6.19 mmol) in ether (30 mL) was added a saturated solution of HCl in ether (20 mL). The mixture was stirred vigorously; a precipitate formed within 15 minutes. After 1 hour, the mixture was filtered, the solids were washed with ether (2×30 mL) and were then pumped dry overnight; a second crop was obtained from the filtrate, giving 0.60 g (54%) of LeuCH2F hydrochloride. Boc-Phe-Gly-LeuOH (synthesized in several steps via mixed anhydride coupling of the appropriate amino acid benzyl esters and subsequent hydrogenolyses, 0.762 g, 1.69 mmol) was dissolved in THF (10 mL), and was cooled to -20° C. NMM (0.186 mL, 1.69 mmol) was added, followed by IBCF (0.219 mL, 1.69 mmol). After 5 minutes, HCl.LeuCH2F (0.31 g, 1.69 mmol) was dissolved in DMF (2 mL), to which solution was added NMM (0.186 mL, 1.69 mmol). This mixture was swirled for approximately 15 seconds and was added to the mixed anhydride solution. After 45 minutes, the reaction was quenched with 1M HCl (20 mL), extracted with ethyl acetate (2×30 mL), the combined organics were washed with saturated aqueous NaHCO3 (30 mL), brine (20 mL), dried over MgSO4, filtered, and evaporated. The thick oil was then dissolved in 1:1 ether/CH2Cl2 (20 mL), and hexane (50 mL) was added. After one day, the supernatant was decanted from the impure product and was evaporated to dryness, yielding 0.14 g of Boc-Phe-Gly-Leu-LeuCH2F.

Workup

  1. waitThis mixture was swirled for approximately 15 seconds
  2. waitAfter 45 minutes
  3. customthe reaction was quenched with 1M HCl (20 mL)
  4. extractionextracted with ethyl acetate (2×30 mL)
  5. washthe combined organics were washed with saturated aqueous NaHCO3 (30 mL), brine (20 mL)
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated
  9. dissolutionThe thick oil was then dissolved in 1:1 ether/CH2Cl2 (20 mL), and hexane (50 mL)
  10. additionwas added
  11. waitAfter one day
  12. customthe supernatant was decanted from the impure product
  13. customwas evaporated to dryness

Sources & evidence

ORD record
ord-c24bcc767122472a8ae2dcbc62341be7
Source dataset
uspto-grants-1992_03
Patent number
US05101068

Reaction notes

Loading…