Dimethylformamide → HCID 22847994, compound

HRID 1655937Notes

Reaction equation

HRID 1655937 reaction equation
[CH2:1]1[O:28][C:4]2([CH2:23][CH2:22][C@@:21]3([CH3:24])[C:6](=[CH:7][CH2:8][C@@H:9]4[C@@H:20]3[CH2:19][CH2:18][C@@:17]3([CH2:25]C#N)[C@H:10]4[CH2:11][CH2:12][C@@H:13]3[C:14](=[O:16])[CH3:15])[CH2:5]2)[O:3][CH2:2]1.[BH4-].[Na+].[C:31]([Si:35](Cl)([CH3:37])[CH3:36])([CH3:34])([CH3:33])[CH3:32].C([N-]C(C)C)(C)C.[Li+].CN(C)C=[O:50]>CN(C)C1C=CN=CC=1.O1CCCC1.CN(C)P(N(C)C)(N(C)C)=O.C(N(CC)CC)C>[CH2:1]1[CH2:2][O:3][C:4]2([CH2:23][CH2:22][C@@:21]3([CH3:24])[C:6](=[CH:7][CH2:8][C@@H:9]4[C@@H:20]3[CH2:19][CH2:18][C@@:17]3([CH:25]=[O:50])[C@H:10]4[CH2:11][CH2:12][C@@H:13]3[CH:14]([O:16][Si:35]([C:31]([CH3:34])([CH3:33])[CH3:32])([CH3:37])[CH3:36])[CH3:15])[CH2:5]2)[O:28]1

Participants

10

Reactant 5

HCID 6228DimethylformamideHCID 28928tert-Butyldimethylsilyl chlorideHCID 2724682Lithium diisopropylamideHCID 4311764Sodium borohydrideHCID 54210594HCID 54210594, compound

Product 1

HCID 22847994HCID 22847994, compound

Reagents, catalysts & solvents 4

HCID 142844-(Dimethylamino)pyridineCatalystHCID 8028TetrahydrofuranSolventHCID 8471TriethylamineSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

The compound 18-cyanopregn-5-ene-3,20-dione 3-ethylene ketal (24) [Freerksen et al., J. Am. Chem. Soc., 99, 1536 (1977)] is reacted with sodium borohydride to reduce the 20-ketone and give a mixture of the two epimeric 20-hydroxy compounds (25). This mixture of alcohols is converted to a mixture of the corresponding (t-butyl)dimethylsilyl ethers (26) by reaction of the alcohols with (t-butyl)dimethylsilyl chloride, 4-dimethylaminopyridine, and triethylamine in dimethylformamide. The resulting 18-cyano silyl ether is then reacted with a strong base, such as lithium diisopropyl amide, in tetrahydrofuran and hexamethylphosphoramide, followed by oxidation and then reaction with a trialkylphosphite, such as trimethyl or triethyl phosphite to give the corresponding 13-carboxaldehyde, i.e., 3,3-ethylenedioxy-20-(t-butyldimethylsilyloxy)pregn-5-en-18-al (27). The aldehyde is then reacted with trimethylsulfonium iodide and sodium dimethyl sulfoxide in a mixture of tetrahydrofuran and dimethyl sulfoxide to give the corresponding 13-oxiranyl compound (28). The silyl protecting group is then removed by treatment of the silyl ether with tetrabutylammonium fluoride to give the free 20-hydroxy compound (29) which is then subjected to a Swern oxidation to give the corresponding 20-ketone (30). The oxirane is then converted to 18-bromomethyl-18-hydroxypregn-4-ene-3,20-dione by reaction with trimethylsilyl bromide followed by dilute acid to give the bromhydrin (31). Alternatively, the oxirane (30) can be reacted with 48% hydrobromic acid in acetone to form the bromohydrin and remove the 3-ketal protecting group simultaneously, and give the desired product (31) directly. The corresponding chlorohydrin or iodohydrin may be prepared by reacting the oxirane with hydrochloric acid or hydroiodic acid, respectively.

Workup

  1. customgive

Sources & evidence

ORD record
ord-4cbc9c97cf2d442a85ec7e00051001c8
Source dataset
uspto-grants-1993_10
Patent number
US05252565

Reaction notes

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