Sodium borohydride → Prednisolone 17,21-diacetate

HRID 446829Notes

Reaction equation

HRID 446829 reaction equation
[C:1]([O:4][CH2:5][C:6]([C@:8]1([O:29][C:30](=[O:32])[CH3:31])[C@:24]2([CH3:25])[C@H:11]([C@H:12]3[C@H:21]([C:22](=[O:26])[CH2:23]2)[C@:20]2([CH3:27])[C:15](=[CH:16][C:17](=[O:28])[CH:18]=[CH:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2].[BH4-].[Na+]>O1CCCC1.CO.Cl>[C:1]([O:4][CH2:5][C:6]([C@:8]1([O:29][C:30](=[O:32])[CH3:31])[C@:24]2([CH3:25])[C@H:11]([C@H:12]3[C@H:21]([C@@H:22]([OH:26])[CH2:23]2)[C@:20]2([CH3:27])[C:15](=[CH:16][C:17](=[O:28])[CH:18]=[CH:19]2)[CH2:14][CH2:13]3)[CH2:10][CH2:9]1)=[O:7])(=[O:3])[CH3:2]

Participants

6

Reactant 2

HCID 4311764Sodium borohydrideHCID 13532419HCID 13532419, compound

Product 1

HCID 14233395Prednisolone 17,21-diacetate

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

To an ice cooled solution of intermediate 2 (2.22 g, 5.0 mmol) in tetrahydrofuran (15 ml) and MeOH (15 ml), sodium borohydride (221 mg, 5.84 mmol) is added in portions over a period of 2.5 hours. The reaction mixture is poured in 1 N HCl and ice (150 ml). The formed precipitate is extracted with AcOEt (3×100 ml), and the combined organic layers are dried over anhydrous Na2SO4 and concentrated. The crude material is crystallized from Ethyl acetate/petroleum ether. The residue from mother liquor is purified by flash chromatography on silica gel, in gradient elution from DCM to DCM/AcOEt 40:60 affording a second crop. The combined crops give the title the compound (1.85 g, 83% total yield).

Workup

  1. extractionThe formed precipitate is extracted with AcOEt (3×100 ml)
  2. dry with materialthe combined organic layers are dried over anhydrous Na2SO4
  3. concentrationconcentrated
  4. customThe crude material is crystallized from Ethyl acetate/petroleum ether
  5. customThe residue from mother liquor is purified by flash chromatography on silica gel, in gradient elution from DCM to DCM/AcOEt 40:60 affording a second crop
  6. customThe combined crops give the title
  7. customthe compound (1.85 g, 83% total yield)

Sources & evidence

ORD record
ord-6d7ac7cedf9f4942b653194f24426033
Source dataset
uspto-grants-2013_07
Patent number
US08481517B2

Reaction notes

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