Sodium Hydroxide → 4-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid hydrochloride

HRID 1909638Notes

Reaction equation

HRID 1909638 reaction equation
C[O:2][C:3](=[O:28])[CH2:4][CH2:5][CH2:6][N:7]1[CH2:11][CH2:10][CH2:9][C@H:8]1[CH2:12][O:13][C:14]1[CH:19]=[CH:18][C:17]([CH2:20][C:21]2[CH:26]=[CH:25][C:24]([Cl:27])=[CH:23][CH:22]=2)=[CH:16][CH:15]=1.[OH-].[Na+]>CO>[ClH:27].[Cl:27][C:24]1[CH:25]=[CH:26][C:21]([CH2:20][C:17]2[CH:16]=[CH:15][C:14]([O:13][CH2:12][C@@H:8]3[CH2:9][CH2:10][CH2:11][N:7]3[CH2:6][CH2:5][CH2:4][C:3]([OH:28])=[O:2])=[CH:19][CH:18]=2)=[CH:22][CH:23]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 690016424-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid methyl ester

Product 1

HCID 689993554-{(S)-2-[4-(4-Chloro-benzyl)-phenoxymethyl]-pyrrolidin-1-yl}-butyric acid hydrochloride

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of the product from step 3 (1.00 g, 2.49 mmol) in MeOH (10 mL) was added 2N NaOH (3.30 mL, 6.60 mmol). The resulting pink solution was stirred at ambient temperature overnight. The solvent was removed in vacuo. The crude oil was dissolved in water (20 mL) and the pH was adjusted to 7 with 2N HCl solution. The crude residue was extracted into ethyl acetate. The combined organic portions were washed with brine, dried over anhydrous Na2SO4, filtered and concentrated in vacuo. The crude product was purified by silica gel flash chromatography using MeOH/dichloromethane (gradient system) to give the free base of the title compound as a yellowish-brown oil. To the subsequent oil was added 2M HCl in diethyl ether (20 mL). The resulting mixture was stirred at ambient temperature for 6 hours. The solvents were decanted. The remaining off-white solid was triturated in diethyl ether (30 mL) overnight. The slurry was filtered, washed with diethyl ether (10 mL×3) and dried in vacuo at 45° C. overnight to afford the title compound as a white solid (0.61 g, 58%). 1H NMR (400 MHz, DMSO-d6); δ 1.72-2.02 (m, 5H), 2.22 (m, 1H), 2.37 (m, 2H), 3.13 (m, 2H), 3.46 (m, 1H), 3.61 (m, 1H), 3.85 (m, 1H), 3.88 (s, 2H), 4.27 (m, 2H), 6.92 (d, J=8.4 Hz, 2H), 7.17 (d, J=8.8 Hz, 2H), 7.22 (d, J=8.4 Hz, 2H), 7.33 (d, J=8.8 Hz, 2H), 10.47 (br s, 1H), 12.33 (br s, 1H); MS (m/z) 388.4 (M+1); LC (100.0%); HPLC (99.5%); Elemental Analysis (Calc) C, 62.27; H, 6.41; N, 3.30 (Found) C, 62.46; H, 6.47; N, 3.26.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionThe crude oil was dissolved in water (20 mL)
  3. extractionThe crude residue was extracted into ethyl acetate
  4. washThe combined organic portions were washed with brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe crude product was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-20881feb90694659a22c507bcb520df6
Source dataset
uspto-grants-2013_12
Patent number
US08598359B2

Reaction notes

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