Acetic Acid → 4-[4-(Tert-butoxycarbonylamino-methyl)piperidin-1-ylmethyl]-piperidine-1-carboxylic acid methyl ester

HRID 1486777Notes

Reaction equation

HRID 1486777 reaction equation
[C:1]([O:5][C:6]([NH:8][CH2:9][CH:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:16][O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH:26]=O)[CH2:22][CH2:21]1)=[O:19].C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[CH3:16][O:17][C:18]([N:20]1[CH2:25][CH2:24][CH:23]([CH2:26][N:13]2[CH2:12][CH2:11][CH:10]([CH2:9][NH:8][C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:7])[CH2:15][CH2:14]2)[CH2:22][CH2:21]1)=[O:19]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 723429Tert-butyl (piperidin-4-ylmethyl)carbamateHCID 5049666Sodium triacetoxyborohydrideHCID 45123041Methyl 4-formylpiperidine-1-carboxylate

Product 1

HCID 668109034-[4-(Tert-butoxycarbonylamino-methyl)piperidin-1-ylmethyl]-piperidine-1-carboxylic acid methyl esterYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-tert-butoxycarbonylaminomethylpiperidine (3.62 g, 16.9 mmol) in dichloromethane (100 mL) was added 4-formylpiperidine-1-carboxylic acid methyl ester (2.89 g, 16.9 mmol) and acetic acid (0.96 mL). The mixture was stirred at room temperature for 10 min prior to the addition of sodium triacetoxyborohydride (5.4 g, 25.5 mmol). The final mixture was stirred at room temperature for 1 h. The reaction was terminated by adding saturated sodium bicarbonate solution (50 mL). The mixture was extracted with dichloromethane (100 mL), and the organic layer was dried over MgSO4. Evaporation of the organic solution afforded a pale yellow oily residue. It was purified by flash silica column chromatography (CH2Cl2 to 5% MeOH/CH2Cl2), yielding the title intermediate (4.4 g). (m/z): [M+H]+ calcd for C19H35N3O4 370.27. found 370.5.

Workup

  1. customThe reaction was terminated
  2. additionby adding saturated sodium bicarbonate solution (50 mL)
  3. extractionThe mixture was extracted with dichloromethane (100 mL)
  4. dry with materialthe organic layer was dried over MgSO4
  5. customEvaporation of the organic solution
  6. customafforded a pale yellow oily residue
  7. customIt was purified by flash silica column chromatography (CH2Cl2 to 5% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-6776262543444784b44b2f12f7d816bf
Source dataset
uspto-grants-2016_08
Patent number
US09428489B2

Reaction notes

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