Hydrochloric Acid → HCID 59201234, compound

HRID 1942296Notes

Reaction equation

HRID 1942296 reaction equation
[Li+].[OH-].[CH3:3][CH:4]([CH3:34])/[CH:5]=[CH:6]\[C@@H: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>[CH3:3][CH:4]([CH3:34])/[CH:5]=[CH:6]\[C@@H: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:25]=[CH:26][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:28][CH:29]=1)[CH2:8][CH2:9][CH:10]([CH3:11])[CH3:12]

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 86639339HCID 86639339, compound

Product 1

HCID 59201234HCID 59201234, compoundYield 85.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of LiOH (60 mg, 2.5 mmol) in H2O (1 ml) was added to a stirred solution of methyl {(2S,4R)-1-[(1S,2Z)-4-methyl-1-(3-methylbutyl)pent-2-en-1-yl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Example 2, Step 1, 210 mg, 0.46 mmol) in THF (2 ml) at RT. The mixture was stirred at RT for 18 hrs, then at 60° C. for 3 hrs. After cooling to RT 2N HCl was added and the THF was removed in vacuo. The residue was partitioned between CH2Cl2 and 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, 4-10% MeOH/CH2Cl2) to give the acid (173 mg) as a colourless foam. 1H NMR (500 MHz, CD3OD): δ 0.69 (3H, d, J 6.6), 0.81-0.87 (9H, m), 1.04-1.18 (2H, m), 1.25 (1H, q, J 12.1), 1.34-1.46 (3H, m), 1.56-1.68 (2H, m), 1.82-1.89 (3H, m), 2.13-2.21 (2H, m), 2.60 (1H, t, J 11.5), 3.23 (1H, brd, J 10), 3.38 (1H, q, J 8.7), 3.63 (1H, d, J 9.6), 5.28 (1H, t, J 10.6), 5.37 (1H, t, J 10.6), 7.53 (2H, d, J 7.7), 7.65 (2H, t, J 8.2); M/Z (ES+) 440 (MH+).

Workup

  1. waitat 60° C. for 3 hrs
  2. additionwas added
  3. customthe THF was removed in vacuo
  4. customThe residue was partitioned between CH2Cl2 and H2O
  5. extractionThe aqueous layer was extracted with CH2Cl2 (×3)
  6. dry with materialThe combined extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified by chromatography (silica, 4-10% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-33dd4cf92c7a488fb061ca8780ebe895
Source dataset
uspto-grants-2013_03
Patent number
US08389547B2

Reaction notes

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