Hydrochloric Acid → HCID 69002371, compound

HRID 2103329Notes

Reaction equation

HRID 2103329 reaction equation
C[O:2][C:3](=[O:27])[CH2:4][CH2:5][CH2:6][N:7]1[CH2:11][CH2:10][C@@H:9]([O:12][C:13]2[CH:18]=[CH:17][C:16]([O:19][C:20]3[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=3)=[CH:15][CH:14]=2)[CH2:8]1.[OH-].[Na+].O.Cl.O1CCOCC1>ClCCl.CO>[ClH:26].[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([O:19][C:16]2[CH:15]=[CH:14][C:13]([O:12][C@@H:9]3[CH2:10][CH2:11][N:7]([CH2:6][CH2:5][CH2:4][C:3]([OH:27])=[O:2])[CH2:8]3)=[CH:18][CH:17]=2)=[CH:21][CH:22]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 312751,4-DioxaneHCID 68998463HCID 68998463, compound

Product 1

HCID 69002371HCID 69002371, compoundYield 94%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
60 °C

Procedure

4-{(R)-3-[4-(4-Chloro-phenoxy)-phenoxy]-pyrrolidin-1-yl}-butyric acid methyl ester (86.8 mg, 0.222 mmol) was taken into 1.029N NaOH solution in water (0.433 mL, 0.445 mmol), and methanol (2 mL). The reaction was sealed and heated to 60° C. and left to react for 24 h. The reaction was concentrated to dryness and taken into 4N HCl in dioxane (0.111 ml, 0.445 mmol) and dichloromethane (1 mL). The reaction was stirred for 15 minutes, and then concentrated to dryness. The residue was taken into dichloromethane and filtered through a syringe filter. The filtrate was then treated with excess 4N HCl in dioxane, stirred for 15 minutes and then concentrated to dryness. The crude product was purified by reverse phase semi-prep HPLC to obtain the title product (43 mg, 47%); LCMS; m/z 376 (M, free amine); 1H NMR (400 MHz, DMSO); δ 1.63-1.70 (m, 2H), 1.74-1.82 (m, 1H), 2.21-2.29 (m, 3H), 2.42-2.45 (m, 3H), 2.62-2.73 (m, 2H), 2.85-2.89 (m, 1H), 4.85 (s, 1H), 6.91-6.96 (m, 4H), 6.98-7.01 (m, 2H), 7.36-7.40 (m, 2H), 8.21 (s, 1H).

Workup

  1. customThe reaction was sealed
  2. waitleft
  3. customto react for 24 h
  4. concentrationThe reaction was concentrated to dryness
  5. concentrationconcentrated to dryness
  6. filtrationfiltered through a syringe
  7. filtrationfilter
  8. additionThe filtrate was then treated with excess 4N HCl in dioxane
  9. stirringstirred for 15 minutes
  10. concentrationconcentrated to dryness
  11. customThe crude product was purified by reverse phase semi-prep HPLC

Sources & evidence

ORD record
ord-b2bd3134ef1b4709a959db8d52542b6e
Source dataset
uspto-grants-2009_08
Patent number
US07576102B2

Reaction notes

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