Benzyl Bromide → Tert-butyl 4-[3-(benzyloxy)-3-oxopropyl]piperidine-1-carboxylate

HRID 643565Notes

Reaction equation

HRID 643565 reaction equation
[CH2:1](Br)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[C:9]([O:13][C:14]([N:16]1[CH2:21][CH2:20][CH:19]([CH2:22][CH2:23][C:24]([OH:26])=[O:25])[CH2:18][CH2:17]1)=[O:15])([CH3:12])([CH3:11])[CH3:10].C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.CCOCC>[CH2:1]([O:26][C:24](=[O:25])[CH2:23][CH2:22][CH:19]1[CH2:18][CH2:17][N:16]([C:14]([O:13][C:9]([CH3:11])([CH3:10])[CH3:12])=[O:15])[CH2:21][CH2:20]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 15125403-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)propanoic acid

Product 1

HCID 59261015Tert-butyl 4-[3-(benzyloxy)-3-oxopropyl]piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent

Procedure

Benzyl bromide (2.29 mL, 19.3 mmol) was added dropwise to a cooled (0° C.) mixture of commercially available 3-[1-(tert-butoxycarbonyl)piperidin-4-yl]propanoic acid (4.96 g, 19.3 mmol) and K2CO3 (6.67 g, 48.3 mmol) in 40 mL of DMF. The reaction mixture was permitted to warm to rt and stir for 3 days (the reaction was likely complete after only a few h). The reaction mixture was diluted with ether and washed four times with water, then once with brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 30% ethyl acetate/hexanes) provided tert-butyl 4-[3-(benzyloxy)-3-oxopropyl]piperidine-1-carboxylate. 1HNMR (CDCl3, 500 MHz): δ 7.38 (m, 5H), 5.14 (s, 2H), 4.09 (br m, 2H), 2.65 (m, 2H), 2.41 (t, J=7.5 Hz, 2H), 1.63 (m, 4H), 1.47 (s, 9H), 1.40 (m, 1H), 1.10 (dq, J=4.0, 12 Hz, 2H).

Workup

  1. temperaturea cooled
  2. washwashed four times with water
  3. dry with materialThe ethereal layer was dried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by MPLC (silica, 30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-fbbceb971ca8402e96687773968c353a
Source dataset
uspto-grants-2010_04
Patent number
US07700591B2

Reaction notes

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