Hydrochloric Acid → HCID 57465823, compound

HRID 420259Notes

Reaction equation

HRID 420259 reaction equation
N1[CH:6]=[CH:5][CH:4]=CC=1.[CH3:7][NH:8][C:9]([C:11]1[CH:20]=[CH:19][C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:21]([C:23]3[N:24]=[CH:25][N:26]([C:28]([C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)([C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)[CH:27]=3)=[O:22])[CH:17]=2)[CH:12]=1)=[O:10].Cl.[C:48]([O:51]CC)(=[O:50])[CH3:49]>O1CCCC1>[OH:22][C@@:21]([C:16]1[CH:15]=[CH:14][C:13]2[C:18](=[CH:19][CH:20]=[C:11]([C:9]([NH:8][CH3:7])=[O:10])[CH:12]=2)[CH:17]=1)([C:23]1[N:24]=[CH:25][N:26]([C:28]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:35]2[CH:36]=[CH:37][CH:38]=[CH:39][CH:40]=2)[C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)[CH:27]=1)[CH2:49][C:48]([O:51][CH2:6][CH2:5][CH3:4])=[O:50]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 1049PyridineHCID 8857Ethyl AcetateHCID 18769037N-methyl-6-((trityl-1H-imidazol-4-yl)carbonyl)-2-naphthamide

Product 1

HCID 57465823HCID 57465823, compoundYield 89%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

Under argon atmosphere, 0.49 g (1.66 mmol, 1.25 equivalents) of (+)-cichonine was added to 6.2 mL (3.3 mmol, 2.5 equivalents) of the solution of n-propyl bromozincacetate in tetrahydrofuran obtained in Example 57 at 3˜4° C. 0.43 mL (5.32 mmol, 4 equivalents) of pyridine was added dropwise at 4˜6° C. The mixture was stirred at 3˜5° C. for 20 minutes. A solution of 0.69 g (1.32 mmol) of N-methyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide in 6.9 mL of THF was added dropwise at −41˜−35° C. 2.5 mL (1.32 mmol, 1 equivalent) of the solution of n-propyl bromozincacetate in tetrahydrofuran obtained in Example 57 was added at −43˜−36° C., and the mixture was stirred at −43˜−37° C. for 2 hours. 10 mL of 1N hydrochloric acid was added at 0° C. or lower, followed by dilution with 30 mL of ethyl acetate. The layers were separated. The organic layer was washed successively. with 5 mL (×3) of 1N hydrochloric acid, 5 mL of water, 5 mL (×2) of an aqueous saturated sodium bicarbonate solution, 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing and concentration under reduced pressure, 2 mL of IPE was added, crystals were loosened, filtered, and washed with 1 mL (×2) of IPE. After washing, vacuum drying (4° C.) to a constant weight afforded 0.73 g of n-propyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate (yield 89%, enantiomer excessive rate 96.0% ee).

Workup

  1. stirringthe mixture was stirred at −43˜−37° C. for 2 hours
  2. customThe layers were separated
  3. washThe organic layer was washed successively
  4. washAfter washing
  5. concentrationconcentration under reduced pressure, 2 mL of IPE
  6. additionwas added
  7. filtrationfiltered
  8. washwashed with 1 mL (×2) of IPE
  9. washAfter washing
  10. customvacuum drying (4° C.) to a constant weight

Sources & evidence

ORD record
ord-f4c9d51735ad4ad792d674be8b4cd06a
Source dataset
uspto-grants-2012_01
Patent number
US08093403B2

Reaction notes

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