Benzaldehyde, 4-(phenylmethoxy)- → HCID 16722958, compound

HRID 222932Notes

Reaction equation

HRID 222932 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[O:22][CH:23]([CH3:25])[CH3:24])[C:5](OC1C(F)=C(F)C(F)=C(F)C=1F)=[O:6].[NH:26]([CH2:28][CH2:29][C:30]#[N:31])[NH2:27].[CH2:32]([O:39][C:40]1[CH:47]=[CH:46][C:43]([CH:44]=O)=[CH:42][CH:41]=1)[C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1.C([BH3-])#N.[Na+].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Cl:1][C:2]1[CH:3]=[C:4]([CH:19]=[CH:20][C:21]=1[O:22][CH:23]([CH3:25])[CH3:24])[C:5]([NH:27][N:26]([CH2:28][CH2:29][C:30]#[N:31])[CH2:44][C:43]1[CH:46]=[CH:47][C:40]([O:39][CH2:32][C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)=[CH:41][CH:42]=1)=[O:6]

Participants

7

Reactant 5

HCID 78109Benzaldehyde, 4-(phenylmethoxy)-2×HCID 136177(2-Cyanoethyl)hydrazineHCID 521998p-Toluenesulfonic acid monohydrate2×HCID 5003444Sodium cyanoborohydride2×HCID 57594128HCID 57594128, compound

Product 1

HCID 16722958HCID 16722958, compoundYield 61.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of pentafluorophenyl 3-chloro-4-[(1-methylethyl)oxy]benzoate (0.100 g, 0.263 mmol) in methanol (5.0 mL) was treated with 3-hydrazinopropanenitrile (0.023 mL, 0.289 mmol) and heated to reflux for 1 h. Following cooling, 4-(benzyloxy)benzaldehyde (0.067 g, 0.315 mmol), sodium cyanoborohydride (0.020 g, 0.315 mmol), and p-toluenesulfonic acid monohydrate (0.060 g, 0.315 mmol) were added and the solution stirred 30 min. at ambient temperature. Additional 4-(benzyloxy)benzaldehyde (0.067 g, 0.315 mmol), sodium cyanoborohydride (0.040 g, 0.637 mmol), and p-toluenesulfonic acid monohydrate (0.100 g, 0.526 mmol) were added and the solution stirred overnight at ambient temperature. The reaction was quenched with 6N aqueous NaOH, diluted with brine, and extracted thrice with EtOAc. The organic layer was dried over MgSO4, filtered, and concentrated in vacuo. Purification via flash column chromatography (30-80% EtOAc/hexanes) gave the title compound as a white solid (0.077 g; 61%). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 7.61 (d, J=2.3 Hz, 1H) 7.45 (dd, J=8.8, 2.2 Hz, 2H) 7.42 (s, 1H) 7.36-7.41 (m, 2H) 7.32 (tt, J=7.0, 1.8 Hz, 1H) 7.28 (s, 1H) 7.17 (br. s., 1H) 6.94 (d, J=8.6 Hz, 2H) 6.88 (d, J=8.6 Hz, 1H) 5.05 (s, 2H) 4.61 (qq, J=6.0 Hz, 1H) 4.22 (s, 2H) 3.39 (t, J=6.6 Hz, 2H) 2.60 (t, J=6.6 Hz, 2H) 1.39 (d, J=6.1 Hz, 6H). MS (ES+) m/e 478 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 1 h
  3. temperatureFollowing cooling
  4. stirringthe solution stirred overnight at ambient temperature
  5. customThe reaction was quenched with 6N aqueous NaOH
  6. additiondiluted with brine
  7. extractionextracted thrice with EtOAc
  8. dry with materialThe organic layer was dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customPurification via flash column chromatography (30-80% EtOAc/hexanes)

Sources & evidence

ORD record
ord-f78a5f83fb3a468ba0b3c2c3bd077237
Source dataset
uspto-grants-2012_06
Patent number
US08207340B2

Reaction notes

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