(R)-tert-butyl 3-(2-(2-ethylphenoxy)benzoyl)piperidine-1-carboxylate → (R)-tert-butyl 3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate

HRID 253555Notes

Reaction equation

HRID 253555 reaction equation
[CH2:1]([C:3]1[CH:30]=[CH:29][CH:28]=[CH:27][C:4]=1[O:5][C:6]1[CH:26]=[CH:25][CH:24]=[CH:23][C:7]=1[C:8]([C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:11]1)=[O:9])[CH3:2].[CH3:31][O:32][CH2:33][CH2:34][CH2:35][CH2:36][Mg]Cl>C1COCC1>[CH2:1]([C:3]1[CH:30]=[CH:29][CH:28]=[CH:27][C:4]=1[O:5][C:6]1[CH:26]=[CH:25][CH:24]=[CH:23][C:7]=1[C@:8]([C@@H:10]1[CH2:15][CH2:14][CH2:13][N:12]([C:16]([O:18][C:19]([CH3:22])([CH3:20])[CH3:21])=[O:17])[CH2:11]1)([OH:9])[CH2:36][CH2:35][CH2:34][CH2:33][O:32][CH3:31])[CH3:2]

Participants

4

Reactant 2

HCID 57786481(R)-tert-butyl 3-(2-(2-ethylphenoxy)benzoyl)piperidine-1-carboxylateHCID 178495008HCID 178495008, compound

Product 1

HCID 57786507(R)-tert-butyl 3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylateYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of (R)-tert-butyl 3-(2-(2-ethylphenoxy)benzoyl)piperidine-1-carboxylate (2.25 g, 4.09 mmol) in THF (7 mL) at −20° C., 4-methoxybutylmagnesium chloride in THF (1.63 M, 5.0 mL, 8.15 mmol) was added dropwise. The resulting solution was warmed to rt slowly, and the completion of reaction was confirmed by LC-MS (˜20 min). The reaction was quenched with satd aq NH4Cl (8 mL) and extracted with ether (4×10 mL). The combined organic layers were washed with water and brine, and solvent was removed under vacuum to give a crude product, which was purified by flash column chromatography to give (R)-tert-butyl 3-((S)-1-(2-(2-ethylphenoxy)phenyl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (1.52 g, 75%). 1H NMR (CDCl3, 400 MHz) δ: 7.52 (d, 1H), 7.26 (dd, 1H), 7.20-7.00 (m, 4H), 6.78 (d, 1H), 6.60 (d, 1H), 4.34 (d, 1H), 4.00 (d, 1H), 3.30 (t, 2H), 3.24 (s, 3H), 2.78 (dd, 1H), 2.64 (q, 2H), 2.62 (m, 1H), 2.40 (m, 1H), 2.26 (m, 1H), 1.92 (m, 1H), 1.56 (m, 4H), 1.40 (s, 9H), 1.30 (m, 3H), 1.22 (t, 3H); MS m/z 520 (M+Na+).

Workup

  1. customthe completion of reaction
  2. customwas confirmed by LC-MS (˜20 min)
  3. customThe reaction was quenched with satd aq NH4Cl (8 mL)
  4. extractionextracted with ether (4×10 mL)
  5. washThe combined organic layers were washed with water and brine, and solvent
  6. customwas removed under vacuum
  7. customto give a crude product, which
  8. customwas purified by flash column chromatography

Sources & evidence

ORD record
ord-7ffe5b5ede04475f9b5f0a0d7753070c
Source dataset
uspto-grants-2011_01
Patent number
US07872028B2

Reaction notes

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