o-Fluorobenzaldehyde → HCID 22064650, compound

HRID 1828111Notes

Reaction equation

HRID 1828111 reaction equation
[NH2:1][C:2]1[CH:27]=[C:26]([C:28]#[N:29])[CH:25]=[CH:24][C:3]=1[CH2:4][NH:5][C:6](=[O:23])[CH:7]([O:20][CH2:21][CH3:22])[N:8]1[C:16](=[O:17])[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][C:14]=2[F:18])[C:9]1=[O:19].[F:30][C:31]1[CH:38]=[CH:37][CH:36]=[CH:35][C:32]=1[CH:33]=O.[BH3-]C#N.[Na+]>CO.[Cl-].[Cl-].[Zn+2]>[C:28]([C:26]1[CH:25]=[CH:24][C:3]([CH2:4][NH:5][C:6](=[O:23])[CH:7]([O:20][CH2:21][CH3:22])[N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][C:14]=3[F:18])[C:9]2=[O:19])=[C:2]([NH:1][CH2:33][C:32]2[CH:35]=[CH:36][CH:37]=[CH:38][C:31]=2[F:30])[CH:27]=1)#[N:29]

Participants

6

Reactant 3

HCID 67970o-FluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 22064712HCID 22064712, compound

Product 1

HCID 22064650HCID 22064650, compoundYield 76%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent2×

Procedure

(RS)-N-(2-amino-4-cyano-benzyl)-2-ethoxy-2-(4-fluoro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetamide (0.060 g) was treated in MeOH (1 ml) successively with 2-fluoro-benzaldehyde (56 mg) and 1 ml of a MeOH-solution containing scrupulously dried ZnCl2 (83 mg) and NaCNBH3 (29 mg). The reaction mixture was stirred for 6 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=6/4) to yield (RS)-N-[4-cyano-2-(2-fluoro-benzylamino)-benzyl ]-2-ethoxy-2-(4-fluoro-1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetamide (58 mg) as yellow oil, MS 505.4 ([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=6/4)

Sources & evidence

ORD record
ord-db8aa210a3b24b2eb7e2548c1e2f2400
Source dataset
uspto-grants-2006_06
Patent number
US07056932B2

Reaction notes

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