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

HRID 1052947Notes

Reaction equation

HRID 1052947 reaction equation
[H-].[Na+].[CH3:3][CH:4]([CH2:6][CH2:7][CH2:8][C@H:9]([C@@H:11]1[C@:29]2([CH3:30])[C@H:14]([C@H:15]3[C@H:26]([CH2:27][CH2:28]2)[C@:24]2([CH3:25])[C:18]([CH2:19][C@H:20]([CH2:22][CH2:23]2)[OH:21])=[CH:17][CH2:16]3)[CH2:13][CH2:12]1)[CH3:10])[CH3:5].Br[CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34].O>O1CCCC1.C(OCC)C>[CH3:5][CH:4]([CH2:6][CH2:7][CH2:8][C@H:9]([C@@H:11]1[C@:29]2([CH3:30])[C@H:14]([C@H:15]3[C@H:26]([CH2:27][CH2:28]2)[C@:24]2([CH3:25])[C:18]([CH2:19][C@@H:20]([O:21][CH2:32][C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])[CH2:22][CH2:23]2)=[CH:17][CH2:16]3)[CH2:13][CH2:12]1)[CH3:10])[CH3:3]

Participants

7

Reactant 4

HCID 962WaterHCID 5997CholesterolHCID 24758Sodium hydrideHCID 79177tert-Butyl bromoacetate

Product 1

HCID 15542405tert-Butyl cholest-5-en-3beta-yloxyacetateYield 26.2%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  1. temperaturethe mixture was refluxed
  2. dry with materialThe combined extracts were dried over anhydrous MgSO4
  3. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-79904852f8844c30b5e61467b9a0c139
Source dataset
uspto-grants-2016_07
Patent number
US09393200B2

Reaction notes

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