1,2-Dichloroethane → Bis(3-fluorophenyl)methyl 1-methylpiperidine-4-carboxylate

HRID 1910515Notes

Reaction equation

HRID 1910515 reaction equation
Cl.[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([C:9]([OH:11])=[O:10])[CH2:5][CH2:4]1.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.[F:26][C:27]1[CH:28]=[C:29]([CH:33]([C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)O)[CH:30]=[CH:31][CH:32]=1.C(N(CC)CC)C>C1COCC1>[CH3:2][N:3]1[CH2:8][CH2:7][CH:6]([C:9]([O:11][CH:33]([C:29]2[CH:30]=[CH:31][CH:32]=[C:27]([F:26])[CH:28]=2)[C:35]2[CH:40]=[CH:39][CH:38]=[C:37]([F:41])[CH:36]=2)=[O:10])[CH2:5][CH2:4]1

Participants

7

Reactant 5

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 2758250Bis(3-fluorophenyl)methanolHCID 27600434-Piperidinecarboxylic acid, 1-methyl-, hydrochloride (1:1)

Product 1

HCID 70925814Bis(3-fluorophenyl)methyl 1-methylpiperidine-4-carboxylateYield 31.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-Methylpiperidine-4-carboxylic acid hydrochloride (250 mg, 1.39 mmol), EDC (400 mg, 2.09 mmol), and HOBT (320 mg, 2.09 mmol) were dissolved in dry THF (10 ml). Bis(3-fluorophenyl)methanol (337 mg, 1.53 mmol) was dissolved in dry THF (4 ml) and then added to the reaction mixture. Triethylamine (6790, 4.87 mmol) was finally added, and the resulting reaction was stirred at room temperature overnight. The reaction was evaporated, and the residue was taken up with EtOAc and washed with water and sat.NaHCO3. The organic phase was dried over sodium sulfate, filtered, and evaporated under vacuum. The crude was purified by flash chromatography (DCM/MeOH=9/1) to afford bis(3-fluorophenyl)methyl 1-methylpiperidine-4-carboxylate (150 mg).

Workup

  1. additionadded to the reaction mixture
  2. customthe resulting reaction
  3. customThe reaction was evaporated
  4. washwashed with water
  5. dry with materialThe organic phase was dried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under vacuum
  8. customThe crude was purified by flash chromatography (DCM/MeOH=9/1)

Sources & evidence

ORD record
ord-e4fcb5cc8dd94d87a273c972c84bc850
Source dataset
uspto-grants-2013_12
Patent number
US08604015B2

Reaction notes

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