Hydrochloric Acid → methyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

HRID 420258Notes

Reaction equation

HRID 420258 reaction equation
[CH3:1][NH:2][C:3]([C:5]1[CH:14]=[CH:13][C:12]2[C:7](=[CH:8][CH:9]=[C:10]([C:15]([C:17]3[N:18]=[CH:19][N:20]([C:22]([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)[C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[CH:21]=3)=[O:16])[CH:11]=2)[CH:6]=1)=[O:4].Cl.[C:42]([O:45][CH2:46]C)(=[O:44])[CH3:43]>C1COCC1>[OH:16][C@@:15]([C:10]1[CH:9]=[CH:8][C:7]2[C:12](=[CH:13][CH:14]=[C:5]([C:3]([NH:2][CH3:1])=[O:4])[CH:6]=2)[CH:11]=1)([C:17]1[N:18]=[CH:19][N:20]([C:22]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH:21]=1)[CH2:43][C:42]([O:45][CH3:46])=[O:44]

Participants

5

Reactant 3

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

Product 1

HCID 57465809methyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoateYield 92%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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 −35˜−40° C. The mixture was stirred at −40˜−35° C. for 1 hour. 2.5 mL (1.32 mmol) of the solution of methyl bromozincacetate in tetrahydrofuran obtained in Example 55 was added dropwise at −40° C., and the mixture was stirred at −40˜−35° C. for 1 hour. 20 mL of 1N hydrochloric acid was added dropwise 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 of 1N hydrochloric acid, 5 mL of water, 5 mL (×2) of an aqueous saturated sodium bicarbonate solution, 5 mL of water, and 5 mL (×2) of an aqueous saturated sodium chloride solution. After washing and concentration under reduced pressure, 4 mL of IPE was added, crystals were loosened, filtered, and washed with 1 mL (×2) of IPE. After washing, vacuum drying (40° C.) to a constant weight afforded 0.72 g of methyl (3S)-3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate (yield 92%, enantiomer excess 93.6% ee).

Workup

  1. stirringthe mixture was stirred at −40˜−35° C. for 1 hour
  2. customThe layers were separated
  3. washThe organic layer was washed successively with 5 mL of 1N hydrochloric acid, 5 mL of water, 5 mL (×2) of an aqueous saturated sodium bicarbonate solution, 5 mL of water, and 5 mL (×2) of an aqueous saturated sodium chloride solution
  4. washAfter washing
  5. concentrationconcentration under reduced pressure, 4 mL of IPE
  6. additionwas added
  7. filtrationfiltered
  8. washwashed with 1 mL (×2) of IPE
  9. washAfter washing
  10. customvacuum drying (40° C.) to a constant weight

Sources & evidence

ORD record
ord-9d6326010ead4dcc97a10dcbcbd8f99c
Source dataset
uspto-grants-2012_01
Patent number
US08093403B2

Reaction notes

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