Methanol → (3S)-3-Amino-3-(4-bromophenyl)propan-1-ol

Temperature

0 °C

Borane-tetrahydrofuran complex (71.7 mL, 71.70 mmol) was added dropwise to a stirred suspension of (S)-3-amino-3-(4-bromophenyl)propanoic acid (3.5 g, 14.34 mmol) in THF (80 mL) at 0° C. over a period of 30 minutes under nitrogen. The resulting suspension was stirred at 0° C. for 30 minutes then at 22° C. for 5 hours. The reaction mixture was added portionwise to methanol (250 mL). The solution was stirred at room temperature for 24 hours. The mixture was concentrated, redissolved in methanol (250 mL) and reconcentrated (this process was repeated three times). The residue was dissolved in DCM (75 mL) and washed with 1N NaOH (50 mL). The aqueous layer was extracted with DCM (3×100 mL) and the extracts combined with the organic layer. The combined organics were washed with saturated brine (50 mL), dried over MgSO4 and concentrated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 2 to 6% MeOH/ammonia in DCM. Pure fractions were evaporated to dryness to afford (S)-3-amino-3-(4-bromophenyl)propan-1-ol (2.160 g, 65.5%) as a colourless gum.

1. waitat 22° C. for 5 hours
2. stirringThe solution was stirred at room temperature for 24 hours
3. concentrationThe mixture was concentrated
4. dissolutionredissolved in methanol (250 mL)
5. dissolutionThe residue was dissolved in DCM (75 mL)
6. washwashed with 1N NaOH (50 mL)
7. extractionThe aqueous layer was extracted with DCM (3×100 mL)
8. washThe combined organics were washed with saturated brine (50 mL)
9. dry with materialdried over MgSO4
10. concentrationconcentrated
11. customto afford crude product
12. customThe crude product was purified by flash silica chromatography, elution gradient 2 to 6% MeOH/ammonia in DCM
13. customPure fractions were evaporated to dryness

ORD record

ord-03691407e0d04784ab4724694d70ed1a

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08101623B2