p-Toluenesulfonic acid → HCID 68845327, compound

HRID 476400Notes

Reaction equation

HRID 476400 reaction equation
[O:1]1[CH:6]=[CH:5][CH2:4][CH2:3][CH2:2]1.C1(C)C=CC(S(O)(=O)=O)=CC=1.[CH2:18]([O:21][C:22]([N:24]1[C:30]2[CH:31]=[C:32]([O:37][CH2:38][CH2:39][CH2:40][C:41]([O:43][CH3:44])=[O:42])[C:33]([O:35][CH3:36])=[CH:34][C:29]=2[C:28](=[O:45])[N:27]2[CH2:46][CH2:47][CH2:48][CH:26]2[CH:25]1[OH:49])=[O:23])[CH:19]=[CH2:20]>CCOC(C)=O>[CH2:18]([O:21][C:22]([N:24]1[C:30]2[CH:31]=[C:32]([O:37][CH2:38][CH2:39][CH2:40][C:41]([O:43][CH3:44])=[O:42])[C:33]([O:35][CH3:36])=[CH:34][C:29]=2[C:28](=[O:45])[N:27]2[CH2:46][CH2:47][CH2:48][C@H:26]2[CH:25]1[O:49][CH:6]1[CH2:5][CH2:4][CH2:3][CH2:2][O:1]1)=[O:23])[CH:19]=[CH2:20]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 80803,4-dihydro-2H-pyranHCID 68843957HCID 68843957, compound

Product 1

HCID 68845327HCID 68845327, compound

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent2×

Procedure

Dihydropyran (4.22 mL, 46.2 mmol) was dissolved in EtOAc (30 mL). This solution was stirred 10 minutes in the presence of para-toluenesulphonic acid (catalytic quantity, 20 mg). 17 (2.0 g, 4.62 mmol) was then added in one portion to this solution and allowed to stir for 2 hours. The solution was diluted with EtOAc (70 mL) and washed with saturated aqueous NaHCO3 (50 mL) followed by brine (50 mL). The organic layer was dried (MgSO4), and the solvent removed under vacuum. The oily residue was dried under vacuum to remove any remaining DHP. It was proved pure by TLC (EtOAc) and 18, was retrieved in quantitative yield, 2.38 g (100%). It was used directly in the next step. 1H NMR (CDCl3) as a mixture of 4/5 of diastereoisomers: δ 7.24-7.21 (2H, s×2), 6.88-6.60 (2H, s×2), 5.89-5.73 (4H, m), 5.15-5.04 (6H, m), 4.96-4.81 (2H, m), 4.68-4.35 (4H, m), 4.12-3.98 (4H, m), 3.98-3.83 (8H, m), 3.74-3.63 (8H, m), 3.60-3.40 (8H, m), 2.56-2.50 (4H, m), 2.23-1.93 (12H, m), 1.92-1.68 (10H, m), 1.66-1.48 (20H, m); 13C NMR (CDCl3) δ 173.4, 167.2, 149.1, 132.0, 114.5, 100.0, 98.4, 94.6, 91.7, 68.0, 67.7, 66.3, 63.9, 63.6, 63.3, 62.9, 56.1, 51.6, 51.5, 46.3, 46.3, 31.1, 30.9, 30.7, 30.4, 30.2, 29.0, 25.4, 25.3, 25.2, 24.2, 20.0, 19.8, 19.7; MS (ES+) m/z (relative intensity) 533.2 ([M+H]+, 100).

Workup

  1. washwashed with saturated aqueous NaHCO3 (50 mL)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent removed under vacuum
  4. customThe oily residue was dried under vacuum
  5. customto remove any remaining DHP
  6. addition1H NMR (CDCl3) as a mixture of 4/5 of diastereoisomers

Sources & evidence

ORD record
ord-401ee9a566154b0d818425a15b601f6d
Source dataset
uspto-grants-2014_01
Patent number
US08637664B2

Reaction notes

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