Hydrochloric Acid → (S)-5-methoxy-1-(2-phenoxyphenyl)-1-((R)-piperidin-3-yl)pentan-1-ol

HRID 1254261Notes

Reaction equation

HRID 1254261 reaction equation
[OH:1][C@@:2]([C@@H:22]1[CH2:27][CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23]1)([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)[CH2:3][CH2:4][CH2:5][CH2:6][O:7][CH3:8].Cl.[OH-].[Na+]>CC#N>[CH3:8][O:7][CH2:6][CH2:5][CH2:4][CH2:3][C@@:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[O:15][C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)([C@@H:22]1[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]1)[OH:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 59382949(R)-tert-butyl 3-((S)-1-hydroxy-5-methoxy-1-(2-phenoxyphenyl)pentyl)piperidine-1-carboxylate

Product 1

HCID 59382957(S)-5-methoxy-1-(2-phenoxyphenyl)-1-((R)-piperidin-3-yl)pentan-1-olYield 100.8%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of (R)-tert-butyl 3-((S)-1-hydroxy-5-methoxy-1-(2-phenoxyphenyl) pentyl)piperidine-1-carboxylate (1.97 g, 4.19 mmol) in MeCN (100 mL) was added 2 N aq HCl (100 mL) slowly at rt. The resulting solution was stirred at rt until no starting material remained (˜16 h), basified to pH=10 with 10 N aq NaOH, and evaporated under reduced pressure to remove MeCN. The aq layer was extracted with CH2Cl2 (4×10 mL). The combined organic layers were washed with brine and dried over Na2SO4. The solvent was removed in vacuo to afford (S)-5-methoxy-1-(2-phenoxyphenyl)-1-((R)-piperidin-3-yl)pentan-1-ol (1.56 g, quantitative) as a free amine.

Workup

  1. custom(˜16 h)
  2. customevaporated under reduced pressure
  3. customto remove MeCN
  4. extractionThe aq layer was extracted with CH2Cl2 (4×10 mL)
  5. washThe combined organic layers were washed with brine
  6. dry with materialdried over Na2SO4
  7. customThe solvent was removed in vacuo

Sources & evidence

ORD record
ord-6a5e03ed20674e6e86f23c57fb71254b
Source dataset
uspto-grants-2013_06
Patent number
US08455521B2

Reaction notes

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