Dihydroxyacetone → 2-(Benzylamino)-2-(6-(benzyloxy)-3,4-dihydronaphthalen-2-yl)propane-1,3-diol

HRID 709916Notes

Reaction equation

HRID 709916 reaction equation
[CH2:1]([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14](B(O)O)[CH2:13][CH2:12]2)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O)C.[OH:25][CH2:26][C:27](=O)[CH2:28][OH:29].[CH2:31]([NH2:38])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>C(Cl)Cl.CO>[CH2:31]([NH:38][C:27]([C:14]1[CH2:13][CH2:12][C:11]2[C:16](=[CH:17][CH:18]=[C:9]([O:8][CH2:1][C:2]3[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=3)[CH:10]=2)[CH:15]=1)([CH2:28][OH:29])[CH2:26][OH:25])[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

6

Reactant 4

HCID 670DihydroxyacetoneHCID 702EthanolHCID 7504BenzylamineHCID 674100386-(Benzyloxy)-3,4-dihydronaphthalen-2-ylboronic acid

Product 1

HCID 674218092-(Benzylamino)-2-(6-(benzyloxy)-3,4-dihydronaphthalen-2-yl)propane-1,3-diolYield 15%

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

The intermediate, 6-(benzyloxy)-3,4-dihydronaphthalen-2-ylboronic acid, from previous step was dissolved in ethanol (400 mL, 7 mol). 1,3-Dihydroxy-2-propanone (6.22 g, 0.0690 mol) was added followed by benzylamine (7.54 mL, 0.0690 mol). The solution turned into a yellow suspension in 1 min. The mixture was stirred at r.t. for 2 hours under an atmosphere of nitrogen. The mixture was filtered. The filtrate was concentrated and the residue was dissolved in EtOAc/MeOH (300 mL/30 mL), washed with saturated NaHCO3/water (50 mL/50 mL) and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic layers were washed with water (50 mL), brine, dried with Na2SO4, filtered, concentrated and dried in high vacuum to give a red-brown solid product as the first crop. The collected solid was dissolved in DCM-MeOH (50 ml/50 mL) and stirred at r.t. overnight under an atmosphere of nitrogen. The solution was concentrated. The residue was treated as the first crop with EtOAc-MeOH-aqueous NaHCO3 to afford the second crop of product (4.40 g, 15%). 1H NMR (CHLOROFORM-d) δ: 6.98-7.66 (m, 13H), 6.77 (br. s., 1H), 5.05 (br. s., 2H), 3.75-4.21 (m, 6H), 2.78 (m, 2H), 1.88-2.54 (m, 2H). MS (M+1): 416.0.

Workup

  1. filtrationThe mixture was filtered
  2. concentrationThe filtrate was concentrated
  3. dissolutionthe residue was dissolved in EtOAc/MeOH (300 mL/30 mL)
  4. washwashed with saturated NaHCO3/water (50 mL/50 mL)
  5. extractionthe aqueous layer was extracted with EtOAc (2×50 mL)
  6. washThe combined organic layers were washed with water (50 mL), brine
  7. dry with materialdried with Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customdried in high vacuum
  11. customto give a red-brown solid product as the first crop
  12. stirringstirred at r.t. overnight under an atmosphere of nitrogen
  13. concentrationThe solution was concentrated
  14. additionThe residue was treated as the first crop with EtOAc-MeOH-aqueous NaHCO3

Sources & evidence

ORD record
ord-051de2fd3b0d4007b7c1b9c4428ccd56
Source dataset
uspto-grants-2015_11
Patent number
US09181191B2

Reaction notes

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