o-Fluorobenzaldehyde → HCID 22064641, compound

HRID 1828106Notes

Reaction equation

HRID 1828106 reaction equation
[NH2:1][C:2]1[CH:26]=[C:25]([C:27]#[N:28])[CH:24]=[CH:23][C:3]=1[CH2:4][NH:5][C:6](=[O:22])[CH:7]([O:19][CH2:20][CH3:21])[N:8]1[CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[CH3:17])[C:9]1=[O:18].[F:29][C:30]1[CH:37]=[CH:36][CH:35]=[CH:34][C:31]=1[CH:32]=O.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[C:27]([C:25]1[CH:24]=[CH:23][C:3]([CH2:4][NH:5][C:6](=[O:22])[CH:7]([O:19][CH2:20][CH3:21])[N:8]2[CH2:16][C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[CH3:17])[C:9]2=[O:18])=[C:2]([NH:1][CH2:32][C:31]2[CH:34]=[CH:35][CH:36]=[CH:37][C:30]=2[F:29])[CH:26]=1)#[N:28]

Participants

6

Reactant 3

HCID 67970o-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22064672HCID 22064672, compound

Product 1

HCID 22064641HCID 22064641, compoundYield 85.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

(RS)-N-(2-Amino-4-cyano-benzyl)-2-ethoxy-2-(4-methyl-1-oxo-1,3-dihydro-isoindol-2-yl)-acetamide (0.101 g) was treated in MeOH (2 ml) successively with 2-fluoro-benzaldehyde (99 mg) and 1 ml of a MeOH-solution containing scrupulously dried ZnCl2 (145 mg) and NaCNBH3 (50 mg). The reaction mixture was stirred for 16 h at 50–55° C., poured onto crashed ice and extracted two times with ethyl acetate. The combined organic layers were washed with water and brine and dried over magnesium sulfate. The solvent was removed under reduced pressure and the residue purified by column chromatography (silica gel, hexane/AcOEt=1/1) to give (RS)-N-[4-cyano-2-(2-fluoro-benzylamino)-benzyl]-2-ethoxy-2-(4-methyl-1-oxo-1,3-dihydro-isoindol-2-yl)-acetamide (111 mg) as colorless oil, MS 487.4 ([M+H]+).

Workup

  1. additionpoured
  2. extractionextracted two times with ethyl acetate
  3. washThe combined organic layers were washed with water and brine
  4. dry with materialdried over magnesium sulfate
  5. customThe solvent was removed under reduced pressure
  6. customthe residue purified by column chromatography (silica gel, hexane/AcOEt=1/1)

Sources & evidence

ORD record
ord-29d7f66a5b1d485eae0cd00143051d4d
Source dataset
uspto-grants-2006_06
Patent number
US07056932B2

Reaction notes

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