Diisopropylamine → ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate

HRID 420217Notes

Reaction equation

HRID 420217 reaction equation
C(NC(C)C)(C)C.C([Li])CCC.[C:13]([O:16][CH2:17][CH3:18])(=[O:15])[CH3:14].[CH3:19][NH:20][C:21]([C:23]1[CH:32]=[CH:31][C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:33]([C:35]3[N:36]=[CH:37][N:38]([C:40]([C:53]4[CH:58]=[CH:57][CH:56]=[CH:55][CH:54]=4)([C:47]4[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=4)[C:41]4[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=4)[CH:39]=3)=[O:34])[CH:29]=2)[CH:24]=1)=[O:22].[Cl-].[NH4+]>CCCCCC.C1COCC1>[OH:34][C:33]([C:28]1[CH:27]=[CH:26][C:25]2[C:30](=[CH:31][CH:32]=[C:23]([C:21]([NH:20][CH3:19])=[O:22])[CH:24]=2)[CH:29]=1)([C:35]1[N:36]=[CH:37][N:38]([C:40]([C:41]2[CH:46]=[CH:45][CH:44]=[CH:43][CH:42]=2)([C:53]2[CH:54]=[CH:55][CH:56]=[CH:57][CH:58]=2)[C:47]2[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=2)[CH:39]=1)[CH2:14][C:13]([O:16][CH2:17][CH3:18])=[O:15]

Participants

8

Reactant 5

HCID 7912DiisopropylamineHCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 18769037N-methyl-6-((trityl-1H-imidazol-4-yl)carbonyl)-2-naphthamideHCID 178418339Butyllithium

Product 1

HCID 57465806ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoateYield 128.7%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Conditions

Temperature
-65 °C

Procedure

Under nitrogen atmosphere, 52.9 mL (0.37 mol, 3 eq) of diisopropylamine was added to 1.3 liters of THF. 234 mL (0.37 mol, 3 eq) of a 1.6 M solution of n-butyllithium in hexane was added dropwise at −65° C. or lower over 23 minutes. After stirred at −65° C. for 20 minutes, 36.6 mL (0.37 mol, 3 eq) of ethyl acetate was added dropwise at −65° C. or lower over 10 minutes. After stirred at −65° C. for 45 minutes, a solution of 65 g (0.13 mol) of N-methyl-6-[(1-trityl-1H-imidazol-4-yl)carbonyl]-2-naphthamide in 260 mL of THF was added dropwise at −65° C. or lower over 25 minutes. The mixture was stirred at −65° C. for 1 hour, and at −4˜−30° C. for 2 hours. After 370 mL of an aqueous saturated ammonium chloride solution was added dropwise at −20° C. or lower, the mixture was warmed to 30° C. After the layers were separated, the organic layer was washed with 370 mL of an aqueous saturated ammonium chloride solution two times. Concentration under reduced pressure afforded 102 g of ethyl 3-hydroxy-3-{6-[(methylamino)carbonyl]-2-naphthyl}-3-(1-trityl-1H-imidazol-4-yl)propanoate.

Workup

  1. stirringAfter stirred at −65° C. for 45 minutes
  2. stirringThe mixture was stirred at −65° C. for 1 hour
  3. waitat −4˜−30° C. for 2 hours
  4. temperaturelower, the mixture was warmed to 30° C
  5. customAfter the layers were separated
  6. washthe organic layer was washed with 370 mL of an aqueous saturated ammonium chloride solution two times
  7. concentrationConcentration under reduced pressure

Sources & evidence

ORD record
ord-4db2c0b69411463aaaf99079caf1b04b
Source dataset
uspto-grants-2012_01
Patent number
US08093403B2

Reaction notes

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