Tetrahydrofuran → HCID 86598011, compound

Temperature

0 °C

A solution of 0.041 mL (0.3 mmol) of diethyl phosphite in 2 mL of THF at 0° C. was treated with 0.32 mL (0.32 mmol) of 1 M sodium bis(trimethyl-silyl)amide in THF. After 20 min, a solution of 92 mg (2 mmol) of 3-(R)-[N-(tert-butoxycarbonyl)amino]-5-(3-methoxy-5-methyl-4-octyloxyphenyl)-pentanal (from Step E) in 3 mL of THF was added. After stirring at 0° C. for 1 h, the reaction was poured into 25 mL of saturated NH4Cl and extracted with 2×25 mL of Et2O. The combined organics were dried over MgSO4 and concentrated. The residue was purified by flash chromatography eluting with a gradient of 3/1 v/v CH2Cl2/CH3CN and 1/1 v/v CH2Cl2/CH3CN to afford 54 mg of the major diastereomer and 12 mg of the minor diastereomer both as colorless films. Major Diastereomer: RF: 0.74 (1/1 v/v CH2Cl2/CH3CN); 1H-NMR (500 MHz) δ 0.91 (t, J=6.9, 3H), 1.31-1.50 (m, 24H), 1.65-1.98 (m, 7H), 2.24 (s, 3H), 2.56-2.69 (m, 2H), 3.83 (s, 3H), 3.86-3.99 (m, 4H), 4.174.25 (m, 4H), 4.48 (d, J=9.1, 1H), 6.54-6.56 (m, 2H); Minor Diastereomer: RF: 0.65 (1/1 v/v CH2Cl2/CH3CN); 1H-NMR (500 MHz) δ 0.90 (t, J=7.0, 3H), 1.30-1.50 (m, 24H),;1.71-1.91 (m, 6H), 2.03 (m, 1H), 2.23 (s, 3H), 2.53-2.66 (m, 2H), 3.02 (br m, 1H), 3.78-3.90 (m, 6H), 4.02 (m, 1H), 4.15-4.22 (m, 4H), 4.78 (m, 1H), 6.54-6.57 (m, 2H).

1. extractionextracted with 2×25 mL of Et2O
2. dry with materialThe combined organics were dried over MgSO4
3. concentrationconcentrated
4. customThe residue was purified by flash chromatography
5. washeluting with a gradient of 3/1 v/v CH2Cl2/CH3CN and 1/1 v/v CH2Cl2/CH3CN
6. customto afford 54 mg of the major diastereomer and 12 mg of the minor diastereomer

ORD record

ord-644911f3d5c84759a52e377d403c07ef

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07309721B2