Benzaldehyde → HCID 10972287, compound

HRID 398197Notes

Reaction equation

HRID 398197 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[CH:5]([NH2:24])[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])([CH3:18])[CH3:17])=[CH:11][CH:10]=1)[CH3:2].[CH:26](=O)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>C(Cl)Cl>[CH2:1]([O:3][C:4](=[O:25])[CH:5]([NH:24][CH2:26][C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1)[CH2:6][CH2:7][O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][C:16]([C:19]([O:21][CH2:22][CH3:23])=[O:20])([CH3:18])[CH3:17])=[CH:11][CH:10]=1)[CH3:2]

Participants

5

Reactant 3

HCID 240BenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 10861143HCID 10861143, compound

Product 1

HCID 10972287HCID 10972287, compoundYield 64.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A sample of 2-amino-4-[4-(1-ethoxycarbonyl-1-methyl-ethoxy)-phenoxy]-butyric acid ethyl ester (612 mg, 1.73 mmol) and benzaldehyde (220 mg, 2.08 mmol) was dissolved in 10 mL of methylene chloride followed by addition of sodium triacetoxyborohydride (550 mg, 2.60 mmol). After 4 hours of stirring at room temperature the reaction mixture was partitioned between additional methylene chloride (50 mL) and 0.1 N HCl (50 mL). The pH of the mixture was then adjusted to ˜13 with 1.0 N NaOH and the layers separated. The aqueous later was extracted with additional methylene chloride (25 mL). The combined organic phases were dried over sodium chloride, then concentrated under reduced pressure. The crude product was purified by silica gel chromatography (ethyl acetate/hexanes) to yield 492 mg of product (64%) as an oil. HPLC RT1=2.78 min; 1H NMR (400 MHz, CDCl3) δ7.28-7.18 (m, 5H), 6.79-6.76 (m, 2H), 6.70-6.68 (m, 2 H), 4.22-4.12 (m, 4H), 4.08-4.02 (m, 1H), 3.99-3.91 (m, 1H), 3.83-3.80 (d, J=12.7 Hz, 1H), 3.65-3.62 (d, J=12.7 Hz, 1H), 3.49-3.47 (m, 1H), 2.17-2.09 (m, 1 H), 2.00-1.92 (m, 1H), 1.49 (s, 6H), 1.26-1.20 (m, 6H).

Workup

  1. customwas partitioned between additional methylene chloride (50 mL) and 0.1 N HCl (50 mL)
  2. customthe layers separated
  3. extractionThe aqueous later was extracted with additional methylene chloride (25 mL)
  4. dry with materialThe combined organic phases were dried over sodium chloride
  5. concentrationconcentrated under reduced pressure
  6. customThe crude product was purified by silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-f2251c0f41884e0298cb03cf5b52c439
Source dataset
uspto-grants-2003_08
Patent number
US06610696B2

Reaction notes

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