Methanol → HCID 131725240, compound

HRID 489215Notes

Reaction equation

HRID 489215 reaction equation
C([O:5]C([N:8]1[CH2:12][C@@H:11]([NH:13][C:14]([NH:16][C:17]2[CH:22]=[C:21]([O:23][CH3:24])[C:20]([O:25][CH3:26])=[C:19]([O:27][CH3:28])[CH:18]=2)=[O:15])[C@H:10]([N:29]2[CH2:34][CH2:33][CH:32]([CH2:35][C:36]3[CH:41]=[CH:40][C:39]([Cl:42])=[CH:38][CH:37]=3)[CH2:31][CH2:30]2)[CH2:9]1)=O)(C)(C)C.CO>Cl.CO>[NH4+:8].[OH-:5].[ClH:42].[ClH:42].[Cl:42][C:39]1[CH:40]=[CH:41][C:36]([CH2:35][CH:32]2[CH2:31][CH2:30][N:29]([C@@H:10]3[CH2:9][NH:8][CH2:12][C@H:11]3[NH:13][C:14]([NH:16][C:17]3[CH:18]=[C:19]([O:27][CH3:28])[C:20]([O:25][CH3:26])=[C:21]([O:23][CH3:24])[CH:22]=3)=[O:15])[CH2:34][CH2:33]2)=[CH:37][CH:38]=1

Participants

5

Reactant 2

HCID 887MethanolHCID 59122976HCID 59122976, compound

Product 2

HCID 14923Ammonium HydroxideHCID 131725240HCID 131725240, compoundYield 198.5%

Reagents, catalysts & solvents 1

HCID 21893726Hydrochloride methanolSolvent

Procedure

A solution of (±)-trans-3-[4-(4-chlorobenzyl)piperidin-1-yl]-4-[3-(3,4,5-trimethoxyphenyl)-ureido]-pyrrolidine-1-carboxylic acid tert-butyl ester (410 mg, 0.68 mmol) in 2% HCl/MeOH (70 mL) was stirred at room temperature overnight. The MeOH was evaporated and the residue was partitioned between CH2Cl2 and saturated NaHCO3. The aqueous phase was extracted with CH2Cl2 and the extracts were washed with brine, dried (MgSO4) and concentrated. Chromatography of the residue on alumina with CH2Cl2 followed by 50:0.95:0.05-5:0.95:0.05 CH2Cl2:MeOH:NH4OH gave the free base (±)-trans-1-{4-[4-(4-chlorobenzyl)piperidin-1-yl]-pyrrolidin-3-yl}-3-(3,4,5-trimethoxyphenyl)urea (225 mg, 0.45 mmol) as a white solid. A solution of the free base (25 mg, 0.05 mmol) in CH2Cl2 was treated with 1 N HCl in Et2O (0.15 mL, 0.15 mmol) and concentrated to give the product (27 mg, 68%) as a yellow solid: mp 157.0-170.0° C.; IR 3416 (br), 2935, 1686, 1606, 1554, 1507 cm−1; 1H NMR [(CD3)2SO] δ 1.50-1.81 (m, 5H), 2.60 (d, J=6.6 Hz, 2H), 3.00-3.99 (m, 20H), 4.68 (m, 1H), 6.76 (s, 2H), 7.21 (m, 2H), 7.32 (m, 2H); MS m/z 504 (M+H)+. Step A: Preparation of (±)-trans-3-[4-(4-chlorobenzyl)piperidin-1-yl]-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Workup

  1. customThe MeOH was evaporated
  2. customthe residue was partitioned between CH2Cl2 and saturated NaHCO3
  3. extractionThe aqueous phase was extracted with CH2Cl2
  4. washthe extracts were washed with brine
  5. dry with materialdried (MgSO4)
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-8fe5d75f31f54f71930b78ce6c984e01
Source dataset
uspto-grants-2005_12
Patent number
US06977265B2

Reaction notes

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