Sodium Hydroxide → HCID 24780865, compound

HRID 1515360Notes

Reaction equation

HRID 1515360 reaction equation
[CH3:1][CH:2]([CH3:34])[CH2:3][CH2:4][C@@H:5]([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)[CH2:6][CH:7]1[CH2:12][CH2:11][O:10][CH2:9][CH2:8]1.[OH-].[Na+]>CO>[CH3:1][CH:2]([CH3:34])[CH2:3][CH2:4][C@@H:5]([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:31])[F:32])=[CH:28][CH:29]=1)[CH2:6][CH:7]1[CH2:8][CH2:9][O:10][CH2:11][CH2:12]1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 57878516HCID 57878516, compound

Product 1

HCID 24780865HCID 24780865, compoundYield 83%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

A solution of the methyl {(2S,4R)-1-[(1R)-4-methyl-1-(tetrahydro-2H-pyran-4-ylmethyl)pentyl]-2-[4-(trifluoromethyl)phenyl]piperidin-4-yl}acetate (Step 1, 142 mg, 0.29 mmol) and aqueous NaOH (4N, 220 μl, 0.88 mmol) in MeOH (2 ml) was heated at 60° C. for 3 hrs. After cooling to RT the MeOH was removed in vacuo, and the residue was partitioned between CH2Cl2/H2O. 2N HCl (˜0.5 ml) was added. The pH of the aqueous layer was adjusted to ˜pH7 with saturated aqueous NaHCO3. The aqueous layer was extracted with CH2Cl2 (×4). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography (silica, 4-8% MeOH/CH2Cl2) to give the acid (113 mg) as a colourless solid. 1H NMR (360 MHz, CD3OD): δ 0.65-0.75 (1H, m), 0.83-1.15 (11H, m), 1.18-1.55 (6H, m), 1.73-1.93 (5H, m), 2.18-2.30 (3H, m), 2.44 (1H, brt, J 12), 3.11 (1H, brd, J 12), 3.35 (1H, d, J 11), 3.43 (1H, d, J 12), 3.79 (2H, d, J 6.7), 3.88 (1H, d, J 8.0), 7.53 (2H, d, J 7.6), 7.63 (2H, d, J 8.2); M/Z (ES+) 470 (MH+).

Workup

  1. customwas removed in vacuo
  2. customthe residue was partitioned between CH2Cl2/H2O
  3. addition2N HCl (˜0.5 ml) was added
  4. extractionThe aqueous layer was extracted with CH2Cl2 (×4)
  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-01903153ca4d4f4c9369ed8a40665888
Source dataset
uspto-grants-2012_07
Patent number
US08222418B2

Reaction notes

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