Hydrochloric Acid → HCID 58815887, compound

HRID 2245881Notes

Reaction equation

HRID 2245881 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:42])[C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([C@@H:19]([N:27]3[CH2:32][C@@H:31]([CH3:33])[N:30]([CH2:34][C:35]4[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=4)[CH2:29][C@@H:28]3[CH3:41])[C:20]3[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=3)[CH:14]=2)[CH2:8][CH2:7]1)=[O:5])C.[OH-].[Na+].Cl.O>C1COCC1.CO>[CH2:34]([N:30]1[C@H:31]([CH3:33])[CH2:32][N:27]([C@@H:19]([C:20]2[CH:25]=[CH:24][CH:23]=[C:22]([OH:26])[CH:21]=2)[C:15]2[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=2)[C:12]([N:9]2[CH2:8][CH2:7][CH:6]([C:4]([OH:5])=[O:3])[CH2:11][CH2:10]2)=[O:42])[C@@H:28]([CH3:41])[CH2:29]1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 12004032HCID 12004032, compound

Product 1

HCID 58815887HCID 58815887, compoundYield 66%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-{3-[(R)-((2S,5R)-4-benzyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (365 mg, Example 122) in THF (4 mL) was added 1N NaOH solution (3 mL). The reaction was stirred at room temperature overnight. The reaction solution was neutralized by the addition of 1 N HCl solution (3 mL). The resulting solution was concentrated under vacuum to give crude product, which was subjected to reverse phase C-18 column chromatography conducted on CombiFlash™ Sq 16×(gradient: 100% H2O to 100% MeOH) to give 1-{3-[(R)-((2S,5R)-4-benzyl-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid (228 mg; 66%). 1H NMR (300 MHz, CD3OD) δ 7.49 (m, 2H), 7.38 (m, 6H), 7.28 (m, 1H), 7.18 (dd, J=8.0, 8.0 Hz, 1H), 6.73 (m, 2H), 6.67 (s, 1H), 5.26 (s, 1H), 4.48 (m, 1H), 4.27 (d, J=13.0 Hz, 1H), 3.66 (m, 2H), 3.13 (m, 1H), 3.01 (m, 2H), 2.85 (m, 2H), 2.68 (m, 1H), 2.49 (m, 2H), 2.13 (dd, J=10.5, 10.5 Hz, 1H), 2.00 (m, 1H), 1.82 (m, 1H), 1.65 (m, 2H), 1.28 (d, J=6.5 Hz, 3H), 1.17 (d, J=6.0 Hz, 3H).

Workup

  1. concentrationThe resulting solution was concentrated under vacuum
  2. customto give crude product, which

Sources & evidence

ORD record
ord-4f3164079464412e9b336a137336cf33
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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