Hydrochloric Acid → {(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acid

HRID 1942295Notes

Reaction equation

HRID 1942295 reaction equation
[Li+].[OH-].[CH3:3][CH:4]([CH3:34])[CH2:5][CH2:6][CH:7]([N:13]1[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]([O:22]C)=[O:21])[CH2:15][C@H:14]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:8][CH2:9][CH:10]([CH3:12])[CH3:11].Cl>O.C1COCC1>[CH3:11][CH:10]([CH3:12])[CH2:9][CH2:8][CH:7]([N:13]1[CH2:18][CH2:17][C@@H:16]([CH2:19][C:20]([OH:22])=[O:21])[CH2:15][C@H:14]1[C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:31])[F:32])=[CH:26][CH:25]=1)[CH2:6][CH2:5][CH:4]([CH3:3])[CH3:34]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 59201267methyl {(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate

Product 1

HCID 59201191{(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetic acidYield 97.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of LiOH (1.6 g, 67 mmol) in H2O (15 ml) was added to a stirred solution of methyl {(2S,4R)-1-[4-methyl-1-(3-methylbutyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Step 1, 6.0 g, 13.2 mmol) in THF (15 ml) at RT. The mixture was stirred and heated at 60° C. for 18 hrs. After cooling to RT 2N HCl (35 ml) was added and the THF was removed in vacuo. The residue was partitioned between CH2Cl2/H2O. The pH of the aqueous layer was adjusted to pH7 with saturated aqueous NaHCO3. The aqueous layer was extracted with CH2Cl2 (×3). The combined extracts were dried (Na2SO4) filtered and evaporated. The residue was purified by chromatography (silica, 4-8% MeOH/CH2Cl2) to give the acid (5.7 g) as a colourless solid. 1H NMR (500 MHz, CD3OD): δ 0.68-0.75 (1H, m), 0.83-0.87 (12H, m), 0.97-1.09 (2H, m), 1.10-1.17 (1H, m), 1.32-1.50 (7H, m), 1.69-1.75 (1H, m), 1.86-2.00 (3H, m), 2.16-2.24 (2H, m), 2.25-2.31 (1H, m), 2.54 (1H, t, J 11.6), 3.17 (1H, d, J 11.8), 3.93 (1H, d, J 10.3), 7.54 (2H, brd, J 7), 7.65 (2H, d, J 8.2); M/Z (ES+) 442 (MH+).

Workup

  1. additionwas added
  2. customthe THF was removed in vacuo
  3. customThe residue was partitioned between CH2Cl2/H2O
  4. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  5. dry with materialThe combined extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by chromatography (silica, 4-8% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-c28a08361a264293b0e9b5a6f2758be4
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

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