4-Methoxybenzaldehyde → (R)-2-(5-bromo-2-fluoro-phenyl)-2-(4-methoxy-benzylamino)-propan-1-ol

HRID 1929499Notes

Reaction equation

HRID 1929499 reaction equation
[NH2:1][C@@:2]([C:6]1[CH:11]=[C:10]([Br:12])[CH:9]=[CH:8][C:7]=1[F:13])([CH3:5])[CH2:3][OH:4].[CH3:14][O:15][C:16]1[CH:23]=[CH:22][C:19]([CH:20]=O)=[CH:18][CH:17]=1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)([O-])O.[Na+]>ClCCCl.C(OCC)(=O)C.CCCCCCC>[Br:12][C:10]1[CH:9]=[CH:8][C:7]([F:13])=[C:6]([C@:2]([NH:1][CH2:20][C:19]2[CH:22]=[CH:23][C:16]([O:15][CH3:14])=[CH:17][CH:18]=2)([CH3:5])[CH2:3][OH:4])[CH:11]=1

Participants

8

Reactant 4

HCID 312444-MethoxybenzaldehydeHCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 58563010(R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol

Product 1

HCID 66931632(R)-2-(5-bromo-2-fluoro-phenyl)-2-(4-methoxy-benzylamino)-propan-1-ol

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 8857Ethyl AcetateSolvent2×HCID 8900HeptaneSolvent

Procedure

A solution of (R)-2-amino-2-(5-bromo-2-fluoro-phenyl)-propan-1-ol (5.0 g, 20.2 mmol) and 4-methoxybenzaldehyde (2.8 g, 20.2 mmol) in 1,2-dichloroethane (150 ml) was treated with sodium triacetoxyborohydride (8.81 g, 40.3 mmol) at room temperature. TLC check (eluent: heptane:ethyl acetate=1:1) showed complete reaction after 30 minutes. For the workup, to the reaction mixture were added ethyl acetate (250 ml) and saturated sodium hydrogen-carbonate solution (100 ml). The aqueous layer was separated, and then extracted with ethyl acetate (250 ml). The combined organic layers were washed with saturated sodium chloride solution (100 ml), thereafter dried over sodium sulfate and evaporated at reduced pressure. After chromatography on Silicycle-Si-amine column using a gradient of heptane and ethyl acetate=100/0 to 50/50 as the eluent, (R)-2-(5-bromo-2-fluoro-phenyl)-2-(4-methoxy-benzylamino)-propan-1-ol was obtained as a colorless oil (7.29 g, 98% of theory). Mass (calculated) C17H19BrFNO2 [368.25]; (found) [M+H]+=368, [M+2-H]+=370.

Workup

  1. customreaction after 30 minutes
  2. customThe aqueous layer was separated
  3. extractionextracted with ethyl acetate (250 ml)
  4. washThe combined organic layers were washed with saturated sodium chloride solution (100 ml)
  5. dry with materialdried over sodium sulfate
  6. customevaporated at reduced pressure

Sources & evidence

ORD record
ord-d5e21c5e32244021b2d6c54bb229dda1
Source dataset
uspto-grants-2012_05
Patent number
US08188079B2

Reaction notes

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