Sodium bis(trimethylsilyl)amide → (2S,5R)-2-tert-Butyl-5-((S)-2-ethyl-pentyl)-3-methyl-4-oxo-tetrahydro-pyrimidine-1-carboxylic Acid Methyl Ester

Temperature

-78 °C

To a −78° C. stirred solution of (S)-2-tert-butyl-3-methyl-4-oxo-tetrahydro-pyrimidine-1-carboxylic acid methyl ester (1.04 g, 4.57 mmol) in dry THF (15 mL) was added NaHMDS (5.03 mL, 1.0 M in THF) dropwise. The reaction was stirred at −78° C. for 1 hour and then a solution of (S)-3-Iodomethyl-hexane (1.24 g, 5.48 mmol) in dry THF (5 mL) was added dropwise. The reaction was stirred at this temperature for 2 hours and than was placed in a −10° C. refrigerator overnight. The reaction was quenched with sat. NH4Cl (20 mL) and was allowed to warm to room temperature. The layers were separated and the aqueous layer was extracted with EtOAc (3×15 mL). The organic extracts were combined and washed with brine (2×15 mL). The organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. The product was purified by chromatography using hexanes/EtOAc (10–>20%) to yield 0.185 g (12%) of pure product: 1H NMR (400 MHz, CD3OD) 8 ppm 0.9 (m, 6 H), 1.3 (m, 5 H), 1.4 (m, 3 H), 1.7 (m, 1 H), 2.5 (m, 1 H), 2.9 (d, J=6.6 Hz, 2 H). MS: M+1 (328).

1. stirringThe reaction was stirred at this temperature for 2 hours
2. customthan was placed in a −10° C.
3. customrefrigerator overnight
4. customThe reaction was quenched with sat. NH4Cl (20 mL)
5. temperatureto warm to room temperature
6. customThe layers were separated
7. extractionthe aqueous layer was extracted with EtOAc (3×15 mL)
8. washwashed with brine (2×15 mL)
9. dry with materialThe organic phase was dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe product was purified by chromatography

ORD record

ord-444f16e6cae34487bd580dc4ef005c8c

Source dataset

uspto-grants-2007_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07179934B2