Benzaldehyde dimethyl acetal → HCID 71153404, compound

HRID 1497297Notes

Reaction equation

HRID 1497297 reaction equation
[OH:1][C@@H:2]1[C@H:7]2[NH:8][C:9](=[O:11])[O:10][C@H:6]2[CH2:5][C@H:4]([CH2:12][OH:13])[C@H:3]1[OH:14].O.[C:16]1([CH3:26])[CH:21]=[CH:20][C:19](S(O)(=O)=O)=[CH:18][CH:17]=1.CO[CH:29]([O:36][CH3:37])[C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1>CN(C=O)C.O>[OH:1][C@@H:2]1[C@H:7]2[N:8]([CH:29]([O:36][CH3:37])[C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:9](=[O:11])[O:10][C@H:6]2[CH2:5][C@@H:4]2[CH2:12][O:13][CH:26]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=3)[O:14][C@@H:3]12

Participants

6

Reactant 3

HCID 62375Benzaldehyde dimethyl acetalHCID 521998p-Toluenesulfonic acid monohydrateHCID 640418HCID 640418, compound

Product 1

HCID 71153404HCID 71153404, compoundYield 735.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of (3aR,4R,5R,6R,7aS)-4,5-dihydroxy-6-(hydroxymethyl)hexahydrobenzo[d]oxazol-2(3H)-one (2.99 g, 14.7 mmol) in DMF (10 mL) at room temperature was added p-toluenesulfonic acid monohydrate (210 mg, 1.10 mmol) followed by benzaldehyde dimethylacetal (6.72 g, 44.2 mmol). The mixture was heated at 60° C. under slightly diminished pressure for 3.5 h. After cooling, the reaction was diluted with water (100 mL) and extracted with EtOAc (2×60 mL). The extracts were washed with brine and dried with MgSO4. The solvent was evaporated to give the crude product. This was purified by silica gel column, eluted with 10-30% EtOAc in hexanes to provide (3aR,4R,4aR,8aR,9aS)-4-hydroxy-3-(methoxy(phenyl)methyl)-6-phenyloctahydro-2H-[1,3]dioxino[5′,4′:4,5]benzo[1,2-d]oxazol-2-one (3.33 g, 55%). MS m/z 434.6 (M+23, 100%); 1H NMR (400 MHz, CDCl3) δ 7.30-7.51 (m, 10H), 6.20 (s, 1H), 5.52 (s, 1H), 4.47-4.50 (m, 1H), 4.24 (dd, J=11.1 Hz, 4.7 Hz, 1H), 4.17 (d, J=2.5 Hz, 1H), 3.83-3.88 (m, 1H), 3.69 (s, 3H), 3.55 (t, J=11.0 Hz, 1H), 3.40 (t, J=10.1 Hz, 1H), 3.26 (t, J=6.8 Hz, 1H), 2.11-2.23 (m, 2H), 1.28-1.36 (m, 1H).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with EtOAc (2×60 mL)
  3. washThe extracts were washed with brine
  4. dry with materialdried with MgSO4
  5. customThe solvent was evaporated
  6. customto give the crude product
  7. customThis was purified by silica gel column
  8. washeluted with 10-30% EtOAc in hexanes

Sources & evidence

ORD record
ord-0787d3dd8fd2412c9ffa0f20cc31ae94
Source dataset
uspto-grants-2015_12
Patent number
US09199949B2

Reaction notes

Loading…