4-Fluorobenzaldehyde → HCID 136078772, compound

HRID 57719Notes

Reaction equation

HRID 57719 reaction equation
Cl.[CH3:2][CH:3]1[CH2:7][NH:6][CH2:5][CH:4]1[C:8]1[NH:13][C:12](=[O:14])[C:11]2=[CH:15][N:16]=[C:17]([CH:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:10]2[N:9]=1.[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[CH:27][CH:26]=1.[BH3-]C#N.[Na+]>ClCCCl.C(O)(=O)C>[F:24][C:25]1[CH:32]=[CH:31][C:28]([CH2:29][N:6]2[CH2:7][CH:3]([CH3:2])[CH:4]([C:8]3[NH:13][C:12](=[O:14])[C:11]4=[CH:15][N:16]=[C:17]([CH:18]5[CH2:23][CH2:22][O:21][CH2:20][CH2:19]5)[N:10]4[N:9]=3)[CH2:5]2)=[CH:27][CH:26]=1

Participants

6

Reactant 3

HCID 680234-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 136480961HCID 136480961, compound

Product 1

HCID 136078772HCID 136078772, compoundYield 21%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 111,2-DichloroethaneSolvent

Procedure

To a solution of compound 9 (80 mg, 0.263 mmol) and 4-fluorobenzaldehyde (326 mg, 2.63 mmol) in 1,2-dichloroethane (15 mL) was added 2 drops of acetic acid. The resulting solution was stirred at room temperature for one hour. Then NaBH3CN (178 mg, 2.63 mmol) was added to the reaction in portions. The resulting mixture was stirred at room temperature for 16 hours. LC-MS showed that the starting material was almost consumed. The reaction mixture was quenched with water (40 mL), and extracted with CH2Cl2 (30 mL×3). The combined organic phases were washed with brine (30 mL), and dried over Na2SO4. After filtered, the filtrate was concentrated in vacuum. The residue was purified by preparative TLC to afford the desired product (20 mg, 21% yield) as a white solid. LC-MS: m/z 412.2 [M+1]+. 1H NMR (400 MHz, CD3OD-d4): δ 8.27 (s, 1H), 7.61 (s, 1H), 7.35˜7.31 (m, 2H), 7.02˜6.98 (m, 2H), 3.96˜3.93 (m, 2H), 3.79˜3.70 (m, 2H), 3.51˜3.39 (m, 3H), 3.15˜3.11 (m, 1H), 3.05˜2.95 (m, 2H), 2.84˜2.79 (m, 1H), 2.61˜2.57 (m, 1H), 2.33˜2.29 (m, 1H), 1.93˜1.87 (m, 2H), 1.80˜1.77 (m, 2H), 1.09 (d, J=6.8 Hz, 3H).

Workup

  1. stirringThe resulting mixture was stirred at room temperature for 16 hours
  2. customwas almost consumed
  3. customThe reaction mixture was quenched with water (40 mL)
  4. extractionextracted with CH2Cl2 (30 mL×3)
  5. washThe combined organic phases were washed with brine (30 mL)
  6. dry with materialdried over Na2SO4
  7. filtrationAfter filtered
  8. concentrationthe filtrate was concentrated in vacuum
  9. customThe residue was purified by preparative TLC

Sources & evidence

ORD record
ord-e61fd8caa29245d3928a978a3b541809
Source dataset
uspto-grants-2016_09
Patent number
US09434733B2

Reaction notes

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