1,4-Dioxane hydrochloride → Racemic 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidine

HRID 1507247Notes

Reaction equation

HRID 1507247 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][C:16]2([F:29])[F:28])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.O1CCOCC1>CO>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([CH:15]2[CH2:20][CH2:19][NH:18][CH2:17][C:16]2([F:29])[F:28])=[CH:11][CH:10]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 204431481,4-Dioxane hydrochlorideHCID 118207308t-Butyl 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidine-1-carboxylate

Product 1

HCID 118207299Racemic 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidineYield 63.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of t-butyl 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidine-1-carboxylate (5.2 g, 12.9 mmol) in MeOH (100 mL) was added 4 M HCl/dioxane (32.2 mL, 130 mmol) and the reaction mixture was stirred at rt for 5 h. The mixture was then evaporated under reduced pressure, and the residue was diluted with a saturated sodium bicarbonate solution and extracted with 200 mL of ethyl acetate. The layers were separated and the organic phase was dried over Na2SO4, filtered, and concentrated under vacuum. The residue was subjected to preparative HPLC (method C) to afford 2.5 grams (63%) of racemic 4-(4-(benzyloxy)phenyl)-3,3-difluoropiperidine. LCMS (method F) RT 2.044 min, m/z 304 (M+H+); 1H NMR (400 MHz, DMSO-d6) δ ppm 7.31-7.48 (m, 5H) 7.21 (d, J=8.53 Hz, 2H) 6.98 (d, J=9.04 Hz, 2H) 5.10 (s, 2H) 3.05-3.20 (m, 2H) 2.98 (d, J=13.05 Hz, 1H) 2.74-2.87 (m, 1H) 2.60 (t, J=11.55 Hz, 1H) 1.88-2.00 (m, 4H) 1.72 (d, J=13.05 Hz, 1H), 19F NMR (377 MHz, DMSO-d6) δ-102.276, -102.900, -115.135, -115.759.

Workup

  1. customThe mixture was then evaporated under reduced pressure
  2. additionthe residue was diluted with a saturated sodium bicarbonate solution
  3. extractionextracted with 200 mL of ethyl acetate
  4. customThe layers were separated
  5. dry with materialthe organic phase was dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-4b0e8dc39cc349afa52669c6a9609010
Source dataset
uspto-grants-2015_12
Patent number
US09221796B2

Reaction notes

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