Water → HCID 67773353, compound

TEA (1.774 mL, 12.80 mmol) was added to (S)-3-methyl-2-(methylamino)butan-1-ol (Compound B2.1) (0.5 g, 4.3 mmol) in DCM (5 mL). The mixture was cooled on an ice-bath and 4-fluoro-3-methylbenzoyl chloride (1.27 mL, 8.96 mmol) in DCM (5 mL) was dropwise (over 5 min) added. The resultant mixture was stirred at rt over night. Additional TEA (0.414 mL, 2.99 mmol) and 4-fluoro-3-methylbenzoyl chloride (0.368 g, 2.13 mmol) was added and the stirring was continued for 3 h. Water (12 mL) was added to the mixture. The organic layer was dried though a phase separator and concentrated. THF (15 mL) and NaOH was added to the residue and the resulting mixture was stirred over night. The mixture was neutralized by the addition of acetic acid. The solvent was removed and DCM (50 mL) was added. The organic phase was washed with Na2CO3 (saturated, 2×30 mL) and brine (30 mL), filtered through a phase separator and concentrated under reduced pressure to give the title compound (0.91 g, 85%). The obtained crude product was used without further purification. Mixture of rotamers: (600 MHz, CD3OD) δ 0.77-0.82, 0.95, 1.02, 1.74-1.83, 1.89-1.97, 2.23-2.31, 2.83, 2.92, 3.37-3.44, 3.58-3.74, 3.79-3.86, 4.23-4.31, 7.01-7.11, 7.18-7.36. Ratio major:minor:1:0.6. Total no of protons: 19.

1. temperatureThe mixture was cooled on an ice-bath
2. custom(over 5 min)
3. additionadded
4. customThe organic layer was dried though a phase separator
5. concentrationconcentrated
6. additionTHF (15 mL) and NaOH was added to the residue
7. additionThe mixture was neutralized by the addition of acetic acid
8. customThe solvent was removed
9. additionDCM (50 mL) was added
10. washThe organic phase was washed with Na2CO3 (saturated, 2×30 mL) and brine (30 mL)
11. filtrationfiltered through a phase separator
12. concentrationconcentrated under reduced pressure

ORD record

ord-e944b387b4cd4891b0d5e3add3febd88

Source dataset

uspto-grants-2013_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08361998B2