Hydrochloric Acid → tert-Butyl (3R)-3-benzoylpiperidine-1-carboxylate

HRID 2355304Notes

Reaction equation

HRID 2355304 reaction equation
CON(C)[C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:7]1)=[O:5].[C:20]1([Mg]Br)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>C1COCC1>[C:4]([C@@H:6]1[CH2:11][CH2:10][CH2:9][N:8]([C:12]([O:14][C:15]([CH3:16])([CH3:17])[CH3:18])=[O:13])[CH2:7]1)(=[O:5])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 30025965(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylateHCID 178418255HCID 178418255, compound

Product 1

HCID 59382841tert-Butyl (3R)-3-benzoylpiperidine-1-carboxylateYield 110%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

(R)-tert-butyl 3-(N-methoxy-N-methylcarbamoyl)piperidine-1-carboxylate (13.6 g, 50 mmol) was dissolved in anhydrous THF (200 mL) and cooled to −10° C. (ice/MeOH bath). Phenylmagnesium bromide solution in THF (100 mL of 1.0 M, 100 mmol, 2 equiv) was added slowly. After 15 min, the reaction mixture was warmed up to rt slowly and stirred for 1 hour. LC-MS showed the reaction was complete. 5% Aq HCl (100 mL) was added slowly to quench the reaction and the mixture was stirred for 20 min. After separation, the aqueous layer was extracted with ether (2×200 mL). The combined organic layers were washed with satd aq NaHCO3 (150 mL), brine (100 mL), and dried over Na2SO4. Concentration afforded crude (R)-tert-butyl 3-benzoylpiperidine-1-carboxylate (16.45 g, 110%) as a clear oil which was used for the next step without further purification. LC-MS (3 min) tR=1.91 min, m/z 302 (M+Na). 1H NMR (CDCl3) δ 7.94 (d, 2H), 7.54 (t, 1H), 7.47 (t, 2H), 4.28 (br d, 1H), 4.09 (d, 1H), 3.38 (t, 1H), 2.92 (br t, 1H), 2.72 (t, 1H), 2.01 (d, 1H), 1.79-1.45 (m, 3H) 1.42 (s, 9H). Chiral HPLC indicated 100% purity.

Workup

  1. customto quench
  2. customthe reaction
  3. stirringthe mixture was stirred for 20 min
  4. customAfter separation
  5. extractionthe aqueous layer was extracted with ether (2×200 mL)
  6. washThe combined organic layers were washed with satd aq NaHCO3 (150 mL), brine (100 mL)
  7. dry with materialdried over Na2SO4
  8. concentrationConcentration

Sources & evidence

ORD record
ord-0f26ee187c9d44269db3e2bda41ccb31
Source dataset
uspto-grants-2010_07
Patent number
US07754737B2

Reaction notes

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