Aluminum(III) Chloride → HCID 57985961, compound

HRID 1869222Notes

Reaction equation

HRID 1869222 reaction equation
[H-].[H-].[H-].[H-].[Li+].[Al+3].[Al+3].[Cl-].[Cl-].[Cl-].O=[C:12]1[C:15]2([CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[CH:14]([C:28]2[CH:33]=[CH:32][C:31]([Cl:34])=[CH:30][CH:29]=2)[N:13]1[CH:35]([CH3:37])[CH3:36]>C1COCC1>[Cl:34][C:31]1[CH:30]=[CH:29][C:28]([CH:14]2[C:15]3([CH2:16][CH2:17][N:18]([C:21]([O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[O:22])[CH2:19][CH2:20]3)[CH2:12][N:13]2[CH:35]([CH3:37])[CH3:36])=[CH:33][CH:32]=1

Participants

5

Reactant 3

HCID 6451240Aluminum(III) ChlorideHCID 21226445Aluminium lithium hydrideHCID 57986056HCID 57986056, compound

Product 1

HCID 57985961HCID 57985961, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, in a dry 500 mL 3-necked flask, add LiAlH4 (0.87 g) and THF (dried over Mol sieves) (96 mL) and cool to 10 C (ice bath). Add AlCl3 (3.33 g) portionwise keeping the temperature at ˜10 C. Heat to 50-60 C for 30 min., then cool to −40 to −50 C, Add 1,1-dimethylethyl 1-oxo-3-(4-chlorophenyl)-2-isopropyl-2,7-diazaspiro[3.5]nonane-7-carboxylate (5.75 g in dry THF (150 mL). Warm the reaction mixture to −20 C and monitor at 15 min intervals until starting material is gone (˜60 min.). At −30 C, quench the reaction mixture at ˜−30 C with 10% NaOH, then warm to room temperature. Extract with diethyl ether (2×300 mL). Extract the diethyl ether with brine, Concentrate the dried (MgSO4) Et2O in vacuo to give the title compound as a viscous oil (9.79 g). Add EtOAc (5 mL) and hexane (25 ml) and let stand at RT to give the title compound as a white solid (0.031 g). Filtrate (4.47 g) in EtOAc (30 mL) and hexane (30 mL) gave additional compound (3.56 g) which was placed on an Analogix system: Column of silica gel (115 g) and eluted with hexane/EtOAc, 20 mL fractions collected. Concentration of fraction 54-145 gave the title compound (2.94 g) as a white solid.

Workup

  1. temperaturecool to 10 C (ice bath)
  2. temperatureHeat to 50-60 C for 30 min.
  3. temperaturecool to −40 to −50 C
  4. temperatureWarm the reaction mixture to −20 C
  5. custom(˜60 min.)
  6. customAt −30 C, quench the reaction mixture at ˜−30 C with 10% NaOH
  7. extractionExtract with diethyl ether (2×300 mL)
  8. extractionExtract the diethyl ether with brine
  9. concentrationConcentrate the
  10. dry with materialdried (MgSO4) Et2O in vacuo

Sources & evidence

ORD record
ord-13b3b598fcd44d89b2eedca453ecc6b6
Source dataset
uspto-grants-2009_12
Patent number
US07638526B2

Reaction notes

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