Acetic Acid → HCID 58815909, compound

HRID 2245882Notes

Reaction equation

HRID 2245882 reaction equation
C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[CH2:15]([O:17][C:18]([CH:20]1[CH2:25][CH2:24][N:23]([C:26](=[O:49])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C@@H:33]([N:41]3[CH2:46][C@@H:45]([CH3:47])[NH:44][CH2:43][C@@H:42]3[CH3:48])[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([OH:40])[CH:35]=3)[CH:28]=2)[CH2:22][CH2:21]1)=[O:19])[CH3:16].[F:50][C:51]1[CH:52]=[C:53]([CH:56]=[CH:57][CH:58]=1)[CH:54]=O.C(O)(=O)C>CN(C)C=O>[CH2:15]([O:17][C:18]([CH:20]1[CH2:25][CH2:24][N:23]([C:26](=[O:49])[C:27]2[CH:32]=[CH:31][CH:30]=[C:29]([C@@H:33]([N:41]3[CH2:46][C@@H:45]([CH3:47])[N:44]([CH2:54][C:53]4[CH:56]=[CH:57][CH:58]=[C:51]([F:50])[CH:52]=4)[CH2:43][C@@H:42]3[CH3:48])[C:34]3[CH:39]=[CH:38][CH:37]=[C:36]([OH:40])[CH:35]=3)[CH:28]=2)[CH2:22][CH2:21]1)=[O:19])[CH3:16]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 680093-FluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 58815986HCID 58815986, compound

Product 1

HCID 58815909HCID 58815909, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium triacetoxyborohydride (1.012 g) was added to a mixture of 1-{3-[(R)-((2S,5R)-2,5-dimethyl-piperazin-1-yl)-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester (916 mg, Example 121), 3-fluorobenzaldehyde (474 mg) and acetic acid (229.4 mg) in dimethylformamide (15 mL). The reaction was stirred under nitrogen at room temperature for 2 hours. The reaction was quenched by the addition of saturated NH4Cl solution (2 mL), followed by the addition of H2O (10 mL). The resulting solution was diluted with 120 mL of H2O to precipitate product. The solution was neutralized with saturated NaHCO3 solution to pH=7 to produce additional precipitate. The mixture was filtered thru a celite pad. The collected solid was rinsed by water (35 mL×2). The solid was dissolved in EtOAc (50 mL) and then eluted from the celite pad. The filtrate (EtOAc solution) was washed with H2O (15 mL×2) and brine (15 mL×1), dried over Na2SO4 and concentrated to give crude product, which was purified by silica gel chromatography conducted on CombiFlash™ Sq 16×(gradient: 100% CH2Cl2 to 10% MeOH in CH2Cl2) to give 1-{3-[(R)-[(2S,5R)-4-(3-fluoro-benzyl)-2,5-dimethyl-piperazin-1-yl]-(3-hydroxy-phenyl)-methyl]-benzoyl}-piperidine-4-carboxylic acid ethyl ester as light pink solid (675 mg; 60%). 1H NMR (300 MHz, CDCl3) δ 7.47 (m, 2H), 7.25 (m, 3H), 7.06 (m, 3H), 6.90 (m, 1H), 6.64 (m, 3H), 5.03 (s, 1H), 4.50 (m, 1H), 4.15 (q, J=7.0 Hz, 2H), 3.91 (d, J=13.5 Hz, 1H), 3.70 (m, 1H), 3.18 (d, J=13.5 Hz, 1H), 3.02 (m, 2H), 2.60 (m, 5H), 2.01 (m, 3H), 1.72 (m, 3H), 1.26 (t, J=7.0 Hz, 3H), 1.05 (m, 6H).

Workup

  1. customThe reaction was quenched by the addition of saturated NH4Cl solution (2 mL)
  2. additionfollowed by the addition of H2O (10 mL)
  3. additionThe resulting solution was diluted with 120 mL of H2O
  4. customto precipitate product
  5. customto produce additional precipitate
  6. filtrationThe mixture was filtered
  7. washThe collected solid was rinsed by water (35 mL×2)
  8. dissolutionThe solid was dissolved in EtOAc (50 mL)
  9. washeluted from the celite pad
  10. washThe filtrate (EtOAc solution) was washed with H2O (15 mL×2) and brine (15 mL×1)
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated
  13. customto give crude product, which
  14. customwas purified by silica gel chromatography

Sources & evidence

ORD record
ord-4e62602fc26547b59b6915489c85a76e
Source dataset
uspto-grants-2010_03
Patent number
US07683168B2

Reaction notes

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