Methylamine → HCID 66872875, compound

HRID 2405994Notes

Reaction equation

HRID 2405994 reaction equation
[CH3:1][NH2:2].[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)([CH:16]=O)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[BH4-].[Na+]>C(O)C>[C:3]([O:7][C:8]([N:10]1[CH2:15][CH2:14][C:13]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)([CH2:16][NH:2][CH3:1])[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4]

Participants

5

Reactant 3

HCID 6329MethylamineHCID 4311764Sodium borohydrideHCID 59840466Tert-butyl 4-(4-chlorophenyl)-4-formylpiperidine-1-carboxylate

Product 1

HCID 66872875HCID 66872875, compoundYield 68%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

A mixture of methylamine in ethanol (18 ml, 33% in ethanol) and 4-(4-chlorophenyl)-4-formyl-piperidine-1-carboxylic acid tert-butyl ester (206 mg, 0.62 mmol) was stirred at room temperature overnight. The solvents were concentrated. The crude material was redissolved in methanol (18 ml) followed by addition of sodium borohydride (49 mg, 1.29 mmol). After stirring for 40 minutes at room temperature, the mixture was partitioned between ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogen carbonate (100 ml). After separation of the two phases the aqueous phase was re-extracted with ethyl acetate (100 ml). The combined organic layers were dried (Na2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 10% methanol in dichloromethane gave 4-(4-chloro-phenyl)-4-methylaminomethyl-piperidine-1-carboxylic acid tert-butyl ester (142 mg, 0.42 mmol, 68%). GC-MS m/z 239 [(M-Boc)+], Rt 5.18 min. 1H NMR (250 MHz, CDCl3): 1.43 (9H, s), 1.80-1.88 (2, m), 2.15-2.24 (2, m), 2.31 (3H, s), 2.81 (2H, s), 2.98-3.09 (2H, m), 3.72-3.78 (2H, m), 7.32 (2H, d, 9 Hz), 7.38 (2H, d, 9 Hz).

Workup

  1. concentrationThe solvents were concentrated
  2. dissolutionThe crude material was redissolved in methanol (18 ml)
  3. stirringAfter stirring for 40 minutes at room temperature
  4. customthe mixture was partitioned between ethyl acetate (100 ml)
  5. customAfter separation of the two phases the aqueous phase
  6. extractionwas re-extracted with ethyl acetate (100 ml)
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. washFlash column chromatography on silica, eluting with 10% methanol in dichloromethane

Sources & evidence

ORD record
ord-6160b8c46c2f40dfbf169f53b579a9ba
Source dataset
uspto-grants-2014_08
Patent number
US08809336B2

Reaction notes

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