4-Bromo-3-fluorobenzaldehyde → (3S,5S)-4-(4-bromo-3-fluorobenzyl)-3,5-dimethylmorpholine

HRID 1924011Notes

Reaction equation

HRID 1924011 reaction equation
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]=O)=[CH:4][C:3]=1[F:10].[CH3:11][C@H:12]1[CH2:17][O:16][CH2:15][C@H:14]([CH3:18])[NH:13]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCl>[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][N:13]2[C@@H:14]([CH3:18])[CH2:15][O:16][CH2:17][C@@H:12]2[CH3:11])=[CH:4][C:3]=1[F:10]

Participants

5

Reactant 3

HCID 27834114-Bromo-3-fluorobenzaldehydeHCID 5049666Sodium triacetoxyborohydrideHCID 11768549(3S,5S)-3,5-Dimethylmorpholine

Product 1

HCID 59543856(3S,5S)-4-(4-bromo-3-fluorobenzyl)-3,5-dimethylmorpholineYield 30.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

4-Bromo-3-fluorobenzaldehyde (0.250 g, 1.23 mmol) and (3S,5S)-3,5-dimethylmorpholine (0.205 g, 1.35 mmol) were dissolved in dichloromethane (10 mL). Sodium triacetoxyborohydride (0.378 g, 1.79 mmol) was added and the mixture was stirred under argon atmosphere at RT for 20 h. The mixture was diluted with dichloromethane and washed with NaHCO3 (aq). The organic phase was dried (MgSO4) and evaporated. The residue was purified by column chromatography on silica eluting with gradients of ammonia in methanol and dichloromethane. The fractions containing product were pooled and evaporated to give (3S,5S)-4-(4-bromo-3-fluorobenzyl)-3,5-dimethylmorpholine (0.113 g, 30%) as a liquid.

Workup

  1. washwashed with NaHCO3 (aq)
  2. dry with materialThe organic phase was dried (MgSO4)
  3. customevaporated
  4. customThe residue was purified by column chromatography on silica eluting with gradients of ammonia in methanol and dichloromethane
  5. additionThe fractions containing product
  6. customevaporated

Sources & evidence

ORD record
ord-a34209d9e5f54100aa7526a2c633288b
Source dataset
uspto-grants-2012_05
Patent number
US08178529B2

Reaction notes

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