Ammonium Chloride → (R)-tert-butyl 3-((S)-1-(benzo[b]thiophen-2-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate

HRID 1254254Notes

Reaction equation

HRID 1254254 reaction equation
[S:1]1[C:5]([C:6]([C@@H:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)=[O:7])=[CH:4][C:3]2[CH:21]=[CH:22][CH:23]=[CH:24][C:2]1=2.[CH3:25][O:26][CH2:27][CH2:28][CH2:29][CH2:30][Mg]Cl.[NH4+].[Cl-]>C1COCC1>[S:1]1[C:5]([C@:6]([C@@H:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[CH2:9]2)([OH:7])[CH2:30][CH2:29][CH2:28][CH2:27][O:26][CH3:25])=[CH:4][C:3]2[CH:21]=[CH:22][CH:23]=[CH:24][C:2]1=2

Participants

5

Reactant 3

HCID 25517Ammonium ChlorideHCID 59382946(R)-tert-butyl 3-(benzo[b]thiophene-2-carbonyl)piperidine-1-carboxylateHCID 178495008HCID 178495008, compound

Product 1

HCID 59382892(R)-tert-butyl 3-((S)-1-(benzo[b]thiophen-2-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylateYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A solution of (R)-tert-butyl 3-(benzo[b]thiophene-2-carbonyl)piperidine-1-carboxylate (146 mg, 0.423 mmol) in dry THF (5 mL) was cooled to −70° C. A solution of 1.34 M 4-methoxybutylmagnesium chloride in THF (630 μL, 2 equiv) was added slowly. After 10 min, the reaction mixture was allowed to warm up to rt slowly and stirred for another 2 h. Sat'd aq NH4Cl (20 mL) was added and the mixture was extracted with ether (2×40 mL). The combined ether layers were washed with brine (20 mL) and dried over Na2SO4. After concentration, the crude product was purified by chromatography on a 12-g silica cartridge eluted with a gradient from 0 to 35% EtOAc in hexanes to afford (R)-tert-butyl 3-((S)-1-(benzo[b]thiophen-2-yl)-1-hydroxy-5-methoxypentyl)piperidine-1-carboxylate (160.7 mg, 88%).

Workup

  1. extractionthe mixture was extracted with ether (2×40 mL)
  2. washThe combined ether layers were washed with brine (20 mL)
  3. dry with materialdried over Na2SO4
  4. concentrationAfter concentration
  5. customthe crude product was purified by chromatography on a 12-g silica cartridge
  6. washeluted with a gradient from 0 to 35% EtOAc in hexanes

Sources & evidence

ORD record
ord-80974cfa31d9440fb475da6f3c613d09
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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