Methanol → HCID 23587466, compound

HRID 489214Notes

Reaction equation

HRID 489214 reaction equation
[Si]([O:8][CH2:9][C@H:10]1[CH2:14][C@@H:13]([NH:15][C:16]([NH:18][C:19]2[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=2)=[O:17])[C@H:12]([N:31]2[CH2:36][CH2:35][CH:34]([CH2:37][C:38]3[CH:43]=[CH:42][C:41]([Cl:44])=[CH:40][CH:39]=3)[CH2:33][CH2:32]2)[CH2:11]1)(C(C)(C)C)(C)C.C(Cl)Cl.CO>Cl.CCO>[NH4+:15].[OH-:8].[ClH:44].[Cl:44][C:41]1[CH:42]=[CH:43][C:38]([CH2:37][CH:34]2[CH2:35][CH2:36][N:31]([C@@H:12]3[CH2:11][C@@H:10]([CH2:9][OH:8])[CH2:14][C@H:13]3[NH:15][C:16]([NH:18][C:19]3[CH:24]=[C:23]([O:25][CH3:26])[C:22]([O:27][CH3:28])=[C:21]([O:29][CH3:30])[CH:20]=3)=[O:17])[CH2:32][CH2:33]2)=[CH:39][CH:40]=1

Participants

6

Reactant 3

HCID 887MethanolHCID 6344DichloromethaneHCID 23587471HCID 23587471, compound

Product 2

HCID 14923Ammonium HydroxideHCID 23587466HCID 23587466, compoundYield 148.6%

Reagents, catalysts & solvents 1

HCID 21887872Ethanol hydrochlorideSolvent

Procedure

A solution of (±)-1-{(1R,2R,4S)-4-(tert-butyl-dimethylsilanyloxymethyl)-2-[4-(4-chlorobenzyl)-piperidin-1-yl]-cyclopentyl}-3-(3,4,5-trimethoxyphenyl)urea (1.13 g, 1.75 mmol) in 1% HCl/EtOH (120 mL) was stirred at room temperature for 1 h. The EtOH 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 with 95:4.75:0.25-90:9.5:0.5 CH2Cl2:MeOH:NH4OH gave the free base (±)-1-{(1R,2R,4S)-2-[4-(4-chlorobenzyl)piperidin-1-yl]-4-hydroxymethyl-cyclopentyl}-3-(3,4,5-trimethoxyphenyl)urea (690 mg, 1.30 mmol) as a yellow solid. A solution of the free base (105 mg, 0.20 mmol) in CH2Cl2 was treated with 1 N HCl in Et2O (0.5 mL, 0.5 mmol) and concentrated to give the product (112 mg, 74%) as a yellow solid: mp 138.0-143.0° C.; IR 3417 (br), 2936, 1687, 1606, 1554, 1507 cm−1; 1H NMR [(CD3)2SO] δ 1.28-2.12 (m, 10H), 2.54 (m, 2H), 2.91 (m, 2H), 3.26-3.59 (m, 8H), 3.71 (s, 6H), 4.34 (m, 1H), 4.70 (br s, 1H), 6.66 (d, J=8.3 Hz, 1H), 6.73 (s, 2H), 7.21 (m, 2H), 7.32 (m, 2H), 8.78 (s, 1H), 10.13 (br s, 1H); MS m/z 532 (M+H)+. Step A: Preparation of (±)-(1R,2R,4R)-4-(tert-butyl-dimethylsilanyloxymethyl)-2-[4-(4-chlorobenzyl)piperidin-1-yl]-cyclopentol

Workup

  1. customThe EtOH 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-c5dc170a6ed54aa094b0a28d9c254e21
Source dataset
uspto-grants-2005_12
Patent number
US06977265B2

Reaction notes

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