Sodium Hydroxide → HCID 86671287, compound

HRID 446642Notes

Reaction equation

HRID 446642 reaction equation
[CH3:1][S:2][S:3][C:4]([CH3:8])([CH3:7])[CH:5]=O.[NH2:9][CH2:10][CH2:11][O:12][C:13]1[CH:18]=[C:17]([CH2:19][OH:20])[N:16]=[C:15]([CH2:21][OH:22])[CH:14]=1.C(OC(NCCOC1C=C(CO)N=C(CO)C=1)=O)(C)(C)C.C([BH3-])#N.[Na+].[OH-].[Na+]>C1COCC1.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].C(O)C>[CH3:7][C:4]([S:3][S:2][CH3:1])([CH3:8])[CH2:5][NH:9][CH2:10][CH2:11][O:12][C:13]1[CH:14]=[C:15]([CH2:21][OH:22])[N:16]=[C:17]([CH2:19][OH:20])[CH:18]=1

Participants

9

Reactant 5

HCID 14798Sodium HydroxideHCID 1062172-(Methyldithio)isobutyraldehyde2×HCID 5003444Sodium cyanoborohydride2×HCID 57570863HCID 57570863, compoundHCID 57570979HCID 57570979, compound

Product 1

HCID 86671287HCID 86671287, compound

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalyst2×HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

270 μl of 2-(methyldithio)isobutyraldehyde and 730 μl of titanium isopropoxide are added to a suspension of 390 mg of 4-[2-aminoethoxy]-2,6-bis(hydroxymethyl)pyridine (prepared after deprotection of the Boc group from 4-(2-(tert-butoxycarbonylamino)ethoxy)-2,6-bis(hydroxymethyl)pyridine described on page 101 of WO 07085930) in 2 ml of THF. After 20 min, an additional 270 μl of 2-(methyldithio)isobutyraldehyde and an additional 730 μl of titanium isopropoxide are added and the mixture is stirred at AT for 2 h. 6 ml of ethanol are then added to the mixture, the mixture is stirred at AT for 20 min and then 124 mg of sodium cyanoborohydride are added to the mixture. After stirring for 45 min, an additional 124 mg of sodium cyanoborohydride are added and, after stirring for 1 h, the mixture is concentrated under RP and the residue is diluted in AcOEt and water. The resulting precipitate is filtered off and dissolved in a 1M aqueous HCl solution. The aqueous phase obtained is brought to basic pH with a 5M aqueous sodium hydroxide solution and extracted three times with DCM, and the combined organic phases are concentrated under RP. 322 mg of 4-[2-(2-methyl-2-(methyldisulphanyl)propylamino)ethoxy]-2,6-bis(hydroxymethyl)pyridine are thus obtained.

Workup

  1. stirringthe mixture is stirred at AT for 20 min
  2. stirringAfter stirring for 45 min
  3. stirringafter stirring for 1 h
  4. concentrationthe mixture is concentrated under RP
  5. additionthe residue is diluted in AcOEt
  6. filtrationThe resulting precipitate is filtered off
  7. dissolutiondissolved in a 1M aqueous HCl solution
  8. customThe aqueous phase obtained
  9. extractionextracted three times with DCM
  10. concentrationthe combined organic phases are concentrated under RP

Sources & evidence

ORD record
ord-8cda285c3a0b48e1b6f96d3ce9751f12
Source dataset
uspto-grants-2013_07
Patent number
US08481042B2

Reaction notes

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