Lithium Hydroxide → 1-((3-Fluoro-4-(5-(phenylmethyl)-1H-indol-2-yl)phenyl)methyl)-3-azetidinecarboxylic acid

HRID 2075221Notes

Reaction equation

HRID 2075221 reaction equation
[CH2:1]([C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][C:12]([C:17]1[CH:31]=[CH:30][C:20]([CH2:21][N:22]3[CH2:25][CH:24]([C:26]([O:28]C)=[O:27])[CH2:23]3)=[CH:19][C:18]=1[F:32])=[CH:11]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[OH-].[Li+]>C1COCC1.O.CC(O)=O>[F:32][C:18]1[CH:19]=[C:20]([CH2:21][N:22]2[CH2:23][CH:24]([C:26]([OH:28])=[O:27])[CH2:25]2)[CH:30]=[CH:31][C:17]=1[C:12]1[NH:13][C:14]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1)=[CH:16][CH:15]=2

Participants

6

Reactant 2

HCID 3939Lithium HydroxideHCID 58415313Methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate

Product 1

HCID 248503621-((3-Fluoro-4-(5-(phenylmethyl)-1H-indol-2-yl)phenyl)methyl)-3-azetidinecarboxylic acid

Reagents, catalysts & solvents 3

HCID 176Acetic AcidSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 1-(4-(5-benzyl-1H-indol-2-yl)-3-fluorobenzyl)azetidine-3-carboxylate (0.090 g, 0.21 mmol) in THF (1.0 mL) and water (1.0 mL) was added lithium hydroxide (0.025 g, 1.1 mmol). The solution was stirred at rt for 1 h, or until starting material was no longer observed by LCMS. The solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0) was added (pH was ca. 9-10). The mixture was acidified with 1N HCl to pH 6.0 and sonicated for 5 min. The aqueous solution was extracted with EtOAc (3×15 mL), and the separated organic extracts were dried over MgSO4, filtered and concentrated to afford a brown oil. The oil was dissolved in AcOH (3.0 mL), and the excess AcOH was removed under reduced pressure. Ether (15 mL) was added, and the resulting precipitate was collected by filtration. The brown solids were washed with water (10 mL) and chloroform (15 mL) to afford title compound as a yellow solid [hS1P1 EC50=1336 nM]. MS (ESI) m/z: Calculated: 414.1; Observed: 415.1 (M++1).

Workup

  1. customThe solvent was removed under reduced pressure, and 0.5M phosphate buffer (3.0 mL, pH 6.0)
  2. additionwas added (pH was ca. 9-10)
  3. customsonicated for 5 min
  4. extractionThe aqueous solution was extracted with EtOAc (3×15 mL)
  5. dry with materialthe separated organic extracts were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto afford a brown oil
  9. customthe excess AcOH was removed under reduced pressure
  10. additionEther (15 mL) was added
  11. filtrationthe resulting precipitate was collected by filtration
  12. washThe brown solids were washed with water (10 mL) and chloroform (15 mL)

Sources & evidence

ORD record
ord-9fa4219f33494ef488dd2118aa506943
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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