Hydrochloric Acid → 7-[({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]heptanoic acid

HRID 446563Notes

Reaction equation

HRID 446563 reaction equation
[F:1][C:2]([F:61])([F:60])[C:3]1[CH:4]=[C:5]([CH:53]=[C:54]([C:56]([F:59])([F:58])[F:57])[CH:55]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([N:40]([CH3:52])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([O:49]CC)=[O:48])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7].[OH-].[Na+].O.Cl>O1CCCC1.CO>[C:47]([O-:49])(=[O:48])[CH3:46].[NH4+:8].[F:59][C:56]([F:57])([F:58])[C:54]1[CH:53]=[C:5]([CH:4]=[C:3]([C:2]([F:1])([F:61])[F:60])[CH:55]=1)[C:6]([N:8]1[CH2:12][C@@:11]([CH2:20][CH2:21][N:22]2[CH2:27][CH2:26][C:25]3([C:35]4[C:30](=[CH:31][CH:32]=[CH:33][CH:34]=4)[CH2:29][C@@H:28]3[O:36][CH2:37][C:38]([N:40]([CH3:52])[CH2:41][CH2:42][CH2:43][CH2:44][CH2:45][CH2:46][C:47]([OH:49])=[O:48])=[O:39])[CH2:24][CH2:23]2)([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][CH:14]=2)[O:10][CH2:9]1)=[O:7]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 962Water2×HCID 14798Sodium HydroxideHCID 86663457Ethyl 7-[({[(2S)-1'-{2-[(5R)-3-[3,5-bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]heptanoate

Product 2

HCID 517165Ammonium AcetateYield 0.1%HCID 866634597-[({[(2S)-1'-{2-[(5R)-3-[3,5-Bis(trifluoromethyl)benzoyl]-5-(4-fluorophenyl)-1,3-oxazolidin-5-yl]ethyl}-2,3-dihydrospiro[indene-1,4'-piperidin]-2-yl]oxy}acetyl)(methyl)amino]heptanoic acidYield 61.9%

Reagents, catalysts & solvents 2

HCID 887MethanolCatalystHCID 8028TetrahydrofuranSolvent

Procedure

The compound (595 mg, 0.901 mmol) obtained in Example 68b was dissolved in tetrahydrofuran (12 mL), a 1 N aqueous sodium hydroxide solution (1.03 mL, 1.03 mmol), water (0.3 mL) and methanol (4 drops) were added, and the mixture was stirred at room temperature. After the reaction was completed, 1 N hydrochloric acid and water were added, the mixture was extracted with methylene chloride, and the resulting organic layer was dried with anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the resulting residue was purified by reverse phase liquid chromatography (XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile:0.1% aqueous ammonium acetate solution, 10:90→100:0, v/v) to give the title compound (233 mg; yield, 40%).

Workup

  1. extractionthe mixture was extracted with methylene chloride
  2. dry with materialthe resulting organic layer was dried with anhydrous sodium sulfate
  3. customThe solvent was evaporated under reduced pressure
  4. customthe resulting residue was purified by reverse phase liquid chromatography (XTerra Prep MS C18 OBD, 5 μm, 30×100 mm) (acetonitrile

Sources & evidence

ORD record
ord-0f387122be1c4ffd93f5362548f9eb74
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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