Water → tert-Butyl cholest-5-en-3beta-yloxyacetate

Participants

Reaction Steps

To a stirred 60% suspension of NaH in mineral oil (400 mg; 3 mmol) under nitrogen a solution of cholesterol (387 mg, 1 mmol) in dry tetrahydrofuran (30 ml) and tert-butyl bromoacetate (585 mg; 3 mmol) was slowly added and the mixture was refluxed under stirring for 16 h. After cooling to room temperature, water (50 ml) was carefully added and the product was taken in diethyl ether (2×50 ml). The combined extracts were dried over anhydrous MgSO4, and concentrated in vacuo. Flash chromatography of the residue on silica gel column (200 ml) in hexane-tert-butyl methyl ether (gradient: 0-30%—tert-butyl methyl ether, 10 ml/min, 160 min) afforded compound tert-Butyl cholest-5-en-3β-yloxyacetate (general formula XII, where n2=1; 131 mg, 26%). 1H NMR (400 MHz, CDCl3) δ (ppm): 5.34-5.38 m, 1H (H-6); 4.01 s, 2H (H-1′); 3.24 tt, J=11.23, 4.56 Hz, 1H (H-3); 2.37-2.43 m, 1H (H-4a); 2.22-2.32 m, 1H (H-4b); 1.76-2.07 m, 5H (CH-1, H-12, H-2, H-7, H-16); 1.48 s, 9H (t-butyl); 1.01 s, 3H (CH3-19); 0.92 d, J=6.60 Hz, 3H (CH3-21); 0.88 d, J=1.80 Hz, 3H (CH3-26); 0.86 d, J=1.80 Hz, 3H (CH3-27); 0.83-1.63 m, 42H (cholesterol+tert-butyl) 0.68 s, 3H (CH3-18); 13C NMR (101 MHz, CDCl3) δ (ppm): 170.11 (C-2′) 140.69 (C-5) 121.78 (C-6) 81.33 (CCH3) 79.81 (C-3) 66.11 (C-1′) 56.80 (C-14) 56.20 (C-17) 50.20 (C-9) 42.35 (C-13) 39.81 (C-12) 39.53 (C-24) 38.79 (C-4) 37.17 (C−1) 36.85 (C-10) 36.21 (C-22) 35.78 (C-20) 31.95 (C-7) 31.92 (C-8) 28.22 (C-2) 28.16 (C-16) 28.12 3C (3×CCH3) 28.00 (C-25) 24.29 (C-15) 23.84 (C-23) 22.80 (C-26) 22.55 (C-27) 21.08 (C-11) 19.35 (C-19) 18.72 (C-21) 11.86 (C-18); for C33H56O3 monoisotopic mass: calculated: 500.4. found: MS ESI m/z: 524.0 [M+Na]+. for C33H56O3—Na+ HR-MS calculated: 523.41217. found: 523.41201; IR (CHCl3): 2954, 2869, 1467, 1457, 1370, 1394, 1161, 1032, 843 (tert-butyl); 1744, 1712, 1125 (C═O); 1670 (C═C); 1125 (C—O); 1181, 1370 (C-26, C-27); 1125 (ether); [α]D −33.7° (c 0.338; CHCl3).

Provenance & Evidence