2,4-Dimethoxybenzaldehyde → (R)-2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propan-1-ol

HRID 920143Notes

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]=[C:22]([O:24][CH3:25])[CH:21]=[CH:20][C:17]=1[CH:18]=O.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[Br:12][C:10]1[CH:9]=[CH:8][C:7]([F:13])=[C:6]([C@:2]([NH:1][CH2:18][C:17]2[CH:20]=[CH:21][C:22]([O:24][CH3:25])=[CH:23][C:16]=2[O:15][CH3:14])([CH3:5])[CH2:3][OH:4])[CH:11]=1

Participants

Conditions

Temperature: 23 °C

Procedure

To a solution of (R)-2-amino-2-(5-bromo-2-fluorophenyl)propan-1-ol (9.2 g, 37.1 mmol, Eq: 1.00) in 1,2-dichloroethane (145 ml) was added at 23° C. 2,4-dimethoxybenzaldehyde (6.16 g, 37.1 mmol, Eq: 1) followed by sodium triacetoxyborohydride (15.7 g, 74.2 mmol, Eq: 2.0). The reaction mixture was stirred at 23° C. overnight. The reaction mixture was extracted with sat NaHCO3/CH2Cl2 twice. The combined organic layers were dried over Na2SO4, filtered off and evaporated totally. The residue was purified by silica gel chromatography with 0-50% EtOAc in heptane to give the (R)-2-(5-bromo-2-fluorophenyl)-2-(2,4-dimethoxybenzylamino)propan-1-ol (14.1 g, 35.4 mmol, 95.5% yield) as a light brown oil. Mass (calculated) C18H21BrFNO3 [398.27]; (found) [M+H]+=398.0, 400.0.

Workup

extractionThe reaction mixture was extracted with sat NaHCO3/CH2Cl2 twice
dry with materialThe combined organic layers were dried over Na2SO4
filtrationfiltered off
customevaporated totally
customThe residue was purified by silica gel chromatography with 0-50% EtOAc in heptane

Sources & evidence

ORD record: ord-b084ed21322645db914d81bdc9744b86
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09273042B2

Reaction notes

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