Ammonium Chloride → tert-Butyl 3-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-2-oxo-1-piperidinecarboxylate

HRID 497574Notes

Reaction equation

HRID 497574 reaction equation
C([N-]C(C)C)(C)C.[Li+].[O:9]=[C:10]1[CH2:15][CH2:14][CH2:13][CH2:12][N:11]1[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17].[C:23]([N:42]1[CH:46]=[C:45]([CH:47]=[O:48])[N:44]=[CH:43]1)([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)([C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=1.[Cl-].[NH4+]>O1CCCC1>[OH:48][CH:47]([C:45]1[N:44]=[CH:43][N:42]([C:23]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([C:30]2[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=2)[C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=2)[CH:46]=1)[CH:15]1[CH2:14][CH2:13][CH2:12][N:11]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[C:10]1=[O:9]

Participants

6

Reactant 4

HCID 25517Ammonium ChlorideHCID 6182331-(triphenylmethyl)-1H-imidazole-4-carbaldehydeHCID 2724682Lithium diisopropylamideHCID 7577838tert-Butyl 2-oxopiperidine-1-carboxylate

Product 1

HCID 22319455tert-Butyl 3-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-2-oxo-1-piperidinecarboxylateYield 99%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Lithium diisopropylamide (8 ml, 1.5M in cyclohexane, 12 mmol) was added dropwise over 5 minutes to a cooled (−78° C.) solution of tert-butyl 2-oxo-1-piperidinecarboxylate (J. Org. Chem. 1983, 48, 2424; J. Chem. Soc. I, 1989, 721) (1.99 g, 10 mmol) in tetrahydrofuran (40 ml), so as to maintain a temperature below −70° C. Once addition was complete, the solution was stirred for 20 minutes. A solution of 1-tritylimidazole-4-carboxaldehyde (J. Med. Chem. 1977, 20, 721) (4.06 g, 12 mmol) in tetrahydrofuran (60 ml) was added slowly, and once addition was complete, the reaction was stirred at −78° C. for 2 hours. Saturated aqueous ammonium chloride solution (50 ml) was added, the mixture allowed to warm to room temperature and then partitioned between water (50 ml) and ethyl acetate (300 ml). The phases were separated, the organic layer dried (MgSO4), filtered, and concentrated under reduced pressure to give the title compound, 5.3 g, 99% yield.

Workup

  1. temperatureso as to maintain a temperature below −70° C
  2. additionOnce addition
  3. additiononce addition
  4. stirringthe reaction was stirred at −78° C. for 2 hours
  5. custompartitioned between water (50 ml) and ethyl acetate (300 ml)
  6. customThe phases were separated
  7. dry with materialthe organic layer dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-f46ee71ff8b24618b78e7824c0926e45
Source dataset
uspto-grants-2005_09
Patent number
US06949577B2

Reaction notes

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