2,2-Dimethoxypropane → 5-tert-Butoxycarbonylamino-5-{2-[4-(5-hydroxyl-1-pentyl)phenyl]ethyl}-2,2-dimethyl-1,3-dioxane

HRID 2059529Notes

Reaction equation

HRID 2059529 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1(/[CH:17]=[CH:18]/[C:19]2[CH:24]=[CH:23][C:22]([C:25]#[C:26][CH2:27][CH2:28][CH2:29][O:30]CC3C=CC=CC=3)=[CH:21][CH:20]=2)[CH2:14][O:13][C:12]([CH3:16])([CH3:15])[O:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].COC(OC)(C)C>CO.CN(C=O)C.C([O-])(O)=O.[Na+].[OH-].[OH-].[Pd+2].C12(CS(O)(=O)=O)C(C)(C)C(CC1)CC2=O>[C:1]([O:5][C:6]([NH:8][C:9]1([CH2:17][CH2:18][C:19]2[CH:20]=[CH:21][C:22]([CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][OH:30])=[CH:23][CH:24]=2)[CH2:10][O:11][C:12]([CH3:16])([CH3:15])[O:13][CH2:14]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 2

HCID 64952,2-DimethoxypropaneHCID 23655183HCID 23655183, compound

Product 1

HCID 236553675-tert-Butoxycarbonylamino-5-{2-[4-(5-hydroxyl-1-pentyl)phenyl]ethyl}-2,2-dimethyl-1,3-dioxaneYield 72.5%

Reagents, catalysts & solvents 5

HCID 18462Bicyclo[2.2.1]heptane-1-methanesulfonic acid, 7,7-dimethyl-2-oxo-, (1S)-CatalystHCID 9942167Palladium hydroxideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Palladium hydroxide on carbon (20%) (36 mg, 0.05 mmol) was added to a solution of 18 (0.361 g, 0.71 mmol) in MeOH (8 mL). Hydrogen was bubbled through the suspension with stirring until 18 was completely consumed and converted to a polar substance (monitored by TLC:hexanes/EtOAc 2:1). The mixture was filtered through a short pad of silica gel and concentrated under vacuum. To a solution of the resulting yellow oil in dry DMF (5 mL) were added 2,2-dimethoxypropane (90.5 mg, 0.84 mmol) and camphorsulfonic acid (10 mg, 0.043 mmol). After the mixture was stirred at room temperature for 1 day, it was diluted with saturated aqueous NaHCO3 solution (15 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic layer was washed sequentially with saturated aqueous NaHCO3 solution (2×20 mL), water (2×20 mL), and brine (20 mL), and was then dried (Na2SO4). The solvent was removed under vacuum, and the residue was purified by chromatography (hexanes/EtOAc 8:1 to 2:1) to give 19 (217 mg, 72%). 1H NMR δ 7.15-7.05 (m, 4H), 5.09 (s, 1H), 3.89 (d, 2H, J=11.6 Hz), 3.67 (d, 2H, J=11.6 Hz), 3.60 (t, 2H, J=6.8 Hz), 2.60-2.50 (m, 4H), 2.40 (br s, 1H), 1.96 (t, 2H, J=8.0 Hz), 1.65-1.36 (m, 21H); 13C NMR δ 154.7, 139.9, 139.0, 128.2, 128.0, 98.2, 79.1, 66.1, 62.4, 51.5, 35.5, 33.5, 32.4, 31.2, 28.4, 28.2, 27.2, 25.3, 19.7. HRMS m/z: calcd for C24H40NO5 (MH+), 422.2901; found, 422.2904.

Workup

  1. customHydrogen was bubbled through the suspension
  2. customwas completely consumed
  3. filtrationThe mixture was filtered through a short pad of silica gel
  4. concentrationconcentrated under vacuum
  5. stirringAfter the mixture was stirred at room temperature for 1 day
  6. extractionextracted with CH2Cl2 (3×20 mL)
  7. washThe combined organic layer was washed sequentially with saturated aqueous NaHCO3 solution (2×20 mL), water (2×20 mL), and brine (20 mL)
  8. dry with materialwas then dried (Na2SO4)
  9. customThe solvent was removed under vacuum
  10. customthe residue was purified by chromatography (hexanes/EtOAc 8:1 to 2:1)

Sources & evidence

ORD record
ord-4401afaca097450d82e751bce3d35467
Source dataset
uspto-grants-2012_10
Patent number
US08277775B2

Reaction notes

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