Methanol → HCID 67142507, compound

HRID 1454412Notes

Reaction equation

HRID 1454412 reaction equation
C[Al](C)C.[NH:5]1[CH2:10][CH2:9][O:8][CH2:7][CH2:6]1.C([O:13][C:14](=O)[C:15]1[CH:20]=[CH:19][C:18]([N:21]2[CH2:25][CH2:24][CH:23]([CH2:26][C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][C:28]=3[N:33]3[CH2:38][CH2:37][N:36]([CH3:39])[CH2:35][CH2:34]3)[C:22]2=[O:40])=[CH:17][CH:16]=1)C.CO>ClCCCl>[CH3:39][N:36]1[CH2:37][CH2:38][N:33]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=2[CH2:26][CH:23]2[CH2:24][CH2:25][N:21]([C:18]3[CH:19]=[CH:20][C:15]([C:14]([N:5]4[CH2:10][CH2:9][O:8][CH2:7][CH2:6]4)=[O:13])=[CH:16][CH:17]=3)[C:22]2=[O:40])[CH2:34][CH2:35]1

Participants

6

Reactant 4

HCID 887MethanolHCID 8083MorpholineHCID 11517401HCID 11517401, compoundHCID 16682925Trimethylaluminum

Product 1

HCID 67142507HCID 67142507, compoundYield 96.1%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent2×

Conditions

Temperature
23 °C

Procedure

Trimethyl aluminum (2 M in toluene, 700 uL, 1.4 mmol) was added dropwise to a solution of morpholine (124 uL, 1.4 mmol) in 1,2-dichloroethane (4 mL) at 0° C. Upon completion of addition, the cold bath was removed and the solution was stirred 30 minutes at 23° C. A solution of 4-{3-[2-(4-methyl-piperazin-1-yl)-benzyl]-2-oxo-pyrrolidin-1yl}-benzoic acid ethyl ester (Example 2, 150 mg, 0.36 mmol) in 1,2-dichloroethane (2 mL) was then added and the solution was heated at 70° C. for ca. 18 hours. The solution was cooled to room temperature, methanol was carefully added to quench excess methyl aluminum species, and the mixture was then treated with sodium sulfate decahydrate (1.5 g). The mixture was stirred rapidly for 3 hours, the salts were filtered off, the solvent was removed in vacuo and the residue was purified by silica gel chromatography (20:1 chloroform-methanol w/1% ammonium hydroxide) to afford 160 mg (96% yield) of the title compound. 13C NMR (100 MHz, CDCl3) d 176.28, 170.23, 152.12, 141.26, 135.00, 130.88, 130.52, 128.25, 127.71, 124.54, 120.84, 119.35, 67.14, 67.09, 55.90, 54.36, 52.97, 46.81, 46.36, 44.91, 32.48, 24.58; MS (AP/Cl) 463.2 (M+H)+. The enantiomers were separated by HPLC (60/40 heptane/ethanol; Chiralcel OJ, 10 cm×50 cm; 27.5 mL/min). Approximate retention times: t1=45 minutes; t2=60 minutes.

Workup

  1. additionUpon completion of addition
  2. customthe cold bath was removed
  3. temperaturethe solution was heated at 70° C. for ca. 18 hours
  4. temperatureThe solution was cooled to room temperature
  5. customto quench excess methyl aluminum species
  6. additionthe mixture was then treated with sodium sulfate decahydrate (1.5 g)
  7. stirringThe mixture was stirred rapidly for 3 hours
  8. filtrationthe salts were filtered off
  9. customthe solvent was removed in vacuo
  10. customthe residue was purified by silica gel chromatography (20:1 chloroform-methanol w/1% ammonium hydroxide)

Sources & evidence

ORD record
ord-08b954bb18d34885bbd6f5384009ca96
Source dataset
uspto-grants-2009_01
Patent number
US07479559B2

Reaction notes

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