Formaldehyde → 4-(3-Bromophenyl)-1-methylpiperidine

HRID 1505917Notes

Reaction equation

HRID 1505917 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([C:14](OC(C)(C)C)=O)[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.C=O>C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:13][CH2:12][N:11]([CH3:14])[CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 712FormaldehydeHCID 40425223tert-Butyl 4-(3-bromophenyl)piperidine-1-carboxylate

Product 1

HCID 534078424-(3-Bromophenyl)-1-methylpiperidineYield 99.3%

Reagents, catalysts & solvents 1

HCID 284Formic AcidSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 4-(3-bromophenyl)-1-N-Boc piperidine (430 mg, 1.26 mmol), formic acid (5 mL) and formaldehyde (0.5 mL) was heated under microwave irradiation at 150° C. for 10 minutes. The cooled reaction mixture was loaded onto a 70 g SCX-2 cartridge which was washed with methanol (200 mL) and then eluted with 2N ammonia in methanol (200 mL). Concentration of the combined basic fractions in vacuo afforded the title compound (318 mg, 99%) as a brown oil. 1H NMR (CDCl3, 300 MHz): 7.38-7.36 (m, 1H); 7.35-7.29 (m, 1H); 7.17-7.14 (m, 2H); 3.03-2.92 (m, 2H); 2.52-2.37 (m, 1H); 2.32 (s, 3H); 2.10-1.99 (m, 2H); 1.87-1.69 (m, 4H).

Workup

  1. customThe cooled reaction mixture
  2. washwas washed with methanol (200 mL)
  3. washeluted with 2N ammonia in methanol (200 mL)

Sources & evidence

ORD record
ord-861815beb0eb48c7bd5abe29508ab513
Source dataset
uspto-grants-2015_12
Patent number
US09216980B2

Reaction notes

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