2,5-Difluorobenzaldehyde → HCID 11479096, compound

HRID 431836Notes

Reaction equation

HRID 431836 reaction equation
[CH2:1]([C:4]1[CH:5]=[N:6][C:7]([N:10]2[CH2:14][C@H:13]([S:15][C:16]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)[C:17]3[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=3)[CH2:12][C@H:11]2[CH2:35][NH2:36])=[N:8][CH:9]=1)[CH2:2][CH3:3].[F:37][C:38]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:39]=1[CH:40]=O.[BH3-]C#N.[Na+]>CO.[Cl-].[Zn+2].[Cl-]>[F:37][C:38]1[CH:45]=[CH:44][C:43]([F:46])=[CH:42][C:39]=1[CH2:40][NH:36][CH2:35][C@@H:11]1[CH2:12][C@@H:13]([S:15][C:16]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)([C:23]2[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=2)[C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][N:10]1[C:7]1[N:8]=[CH:9][C:4]([CH2:1][CH2:2][CH3:3])=[CH:5][N:6]=1

Participants

6

Reactant 3

HCID 1376632,5-DifluorobenzaldehydeHCID 5003444Sodium cyanoborohydrideHCID 11352413HCID 11352413, compound

Product 1

HCID 11479096HCID 11479096, compoundYield 93%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 887MethanolSolvent3×

Procedure

To 643 mg (1.3 mmol) (2S,4R)-C-[1-(5-Propyl-pyrimidin-2-yl)-4-tritylsulfanyl-pyrrolidin-2-yl]-methylamine in 3 ml methanol were added 158 μl (1.43 mmol) 2,5-difluorobenzaldehyde and 5 ml methanol to partially redissolve the compound. This was followed by a solution of 108 mg (0.78 mmol) zinc chloride and 109 mg (1.56 mmol) NaBH3CN in 3 ml methanol. The solution was stirred over night, concentrated and dissolved in ETOAc/sat NaHCO3 solution. The inorganic layer was extracted with EtOAc, the combined organic layers were washed with NaHCO3 and brine, dried over Na2SO4 and evaporated. Purification with column chromatography yielded 750 mg (93%) (2S,4R)-(2,5-Difluoro-benzyl)-[1-(5-propyl-pyrimidin-2-yl)-4-tritylsulfanyl-pyrrolidin-2-ylmethyl]-amine as light yellow gum, MS: 621 (MH+).

Workup

  1. dissolutionto partially redissolve the compound
  2. concentrationconcentrated
  3. dissolutiondissolved in ETOAc/sat NaHCO3 solution
  4. extractionThe inorganic layer was extracted with EtOAc
  5. washthe combined organic layers were washed with NaHCO3 and brine
  6. dry with materialdried over Na2SO4
  7. customevaporated
  8. customPurification with column chromatography

Sources & evidence

ORD record
ord-da0e4042be67451a9d972c6b7a8b9733
Source dataset
uspto-grants-2003_12
Patent number
US06660738B2

Reaction notes

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