Methanol → Becocalcidiol

HRID 1929323Notes

Reaction equation

HRID 1929323 reaction equation
[CH3:1][C@@H:2]([C@@H:10]1[C@@:14]2([CH3:29])[CH2:15][CH2:16][CH2:17]/[C:18](=[CH:19]\[CH:20]=[C:21]3\[CH2:22][C@@H:23]([OH:28])[CH2:24][CH2:25][C:26]\3=C)/[C@@H:13]2[CH2:12][CH2:11]1)/[CH:3]=[CH:4]/[C@@H](C(C)C)C.[BH4-].[Na+].[CH3:32][OH:33]>N1C=CC=CC=1>[CH3:4][CH2:3][C@@H:2]([C@@H:10]1[C@@:14]2([CH3:29])[CH2:15][CH2:16][CH2:17]/[C:18](=[CH:19]\[CH:20]=[C:21]3[CH2:26][C@@H:32]([OH:33])[C:24](=[CH2:25])[C@H:23]([OH:28])[CH2:22]3)/[C@@H:13]2[CH2:12][CH2:11]1)[CH3:1]

Participants

5

Reactant 3

HCID 887MethanolHCID 4311764Sodium borohydride3×HCID 5280793Ergocalciferol

Product 1

HCID 5289547BecocalcidiolYield 76%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

A solution of vitamin D2 (5 g, 12.7 mmol) in methanol (400 mL) and pyridine (5 mL) was cooled to −78° C. while purging with argon. The argon stream was stopped and a stream of ozone was passed until a blue color appeared. The solution was purged with oxygen until the blue color disappeared and treated with NaBH4 (1.2 g, 32 mmol). After 20 minutes, the second portion of NaBH4 (1.2 g, 32 mmol) was added and reaction was allowed to warm to room temperature. The third portion of NaBH4 (1.2 g, 32 mmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction was quenched with 70 mL of water and concentrated under vacuum. The residue was extracted with methylene chloride (3×100 mL). The organic phase was washed with 1M aqueous solution of HCl (2×100 mL), saturated aqueous solution of NaHCO3 (100 mL), dried over anhydrous MgSO4 and concentrated under vacuum. The residue was purified by flash chromatography (25% ethyl acetate/hexane) to yield 2.05 g (9.69 mmol, 76% yield) of diol 1 as white crystals. [α]D+56.0 (c 0.95, CHCl3); mp 110-111° C.; 1H NMR (400 MHz, CDCl3) δ 0.96 (3H, s), 1.03 (3H, d, J=6.6 Hz), 3.38 (1H, dd, J=10.5 Hz, J=6.8 Hz), 3.64 (1H, dd, J=10.5 Hz, J=3.2 Hz), 4.09 (1H, d, J=2.3 Hz); 13C NMR (100 MHz, CDCl3) δ 13.6, 16.6, 17.4, 22.6, 26.6, 33.5, 38.2, 40.2, 41.3, 52.3, 52.9, 67.8, 69.2; MS (EI) m/z 212 (2, M+), 194 (17), 179 (18), 163 (10), 135 (19), 125 (34), 111 (100); exact mass calculated for C13H22O ([M−H2O]+) 194.1671, found 194.1665.

Workup

  1. customwhile purging with argon
  2. customThe solution was purged with oxygen until the blue color
  3. customreaction
  4. customThe reaction was quenched with 70 mL of water
  5. concentrationconcentrated under vacuum
  6. extractionThe residue was extracted with methylene chloride (3×100 mL)
  7. washThe organic phase was washed with 1M aqueous solution of HCl (2×100 mL), saturated aqueous solution of NaHCO3 (100 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. concentrationconcentrated under vacuum
  10. customThe residue was purified by flash chromatography (25% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-dce874156711410a8b600160f95905dd
Source dataset
uspto-grants-2012_05
Patent number
US08188064B2

Reaction notes

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