Hydrochloric Acid → HCID 58815940, compound

HRID 2245883Notes

Reaction equation

HRID 2245883 reaction equation
C([O:3][C:4]([CH:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:43])[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]=[C:37]([F:41])[CH:36]=4)[CH2:29][C@@H:28]3[CH3:42])[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>[F:41][C:37]1[CH:36]=[C:35]([CH:40]=[CH:39][CH:38]=1)[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:43])[C@@H:28]([CH3:42])[CH2:29]1

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 14798Sodium HydroxideHCID 58815909HCID 58815909, compound

Product 1

HCID 58815940HCID 58815940, compoundYield 41.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 1-{3-[(R)-[(2S,5R)-4-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (463 mg, Example 124) 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-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxyphenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid (183 mg; 41%). 1H NMR (300 MHz, CD3OD) δ 7.48 (m, 2H), 7.37 (m, 2H), 7.27 (m, 1H), 7.16 (m, 3H), 7.04 (m, 1H), 6.71 (m, 3H), 5.21 (s, 1H), 4.47 (m, 1H), 4.13 (d, J=13.5 Hz, 1H), 3.66 (m, 1H), 3.51 (d, J=13.5 Hz, 1H), 3.09 (m, 2H), 2.81 (m, 3H), 2.68 (m, 1H), 2.55 (m, 1H), 2.30 (m, 1H), 2.06 (m, 2H), 1.83 (m, 1H), 1.65 (m, 2H), 1.21 (d, J=6.0 Hz, 3H), 1.15 (d, J=6.5 Hz, 3H).

Workup

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

Sources & evidence

ORD record
ord-23d68ce464984e17a540aab707026dcf
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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