Sodium hydride → 2-[7-Isocyano-2,12-dimethyl-2, 12-di-p-tolyl-13-(tetrahydropyran-2-yloxy)-7-(toluene-4-sulfonyl)-tridecanyloxy]-tetrahydropyran

HRID 47985Notes

Reaction equation

HRID 47985 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([CH3:22])([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)[CH2:7][O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1.[C:23]1([CH3:35])[CH:28]=[CH:27][C:26]([S:29]([CH2:32][N+:33]#[C-:34])(=[O:31])=[O:30])=[CH:25][CH:24]=1.[H-].[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O.C(OCC)C>[N+:33]([C:32]([S:29]([C:26]1[CH:25]=[CH:24][C:23]([CH3:35])=[CH:28][CH:27]=1)(=[O:30])=[O:31])([CH2:2][CH2:3][CH2:4][CH2:5][C:6]([CH3:22])([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)[CH2:7][O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1)[CH2:2][CH2:3][CH2:4][CH2:5][C:6]([CH3:22])([C:15]1[CH:20]=[CH:19][C:18]([CH3:21])=[CH:17][CH:16]=1)[CH2:7][O:8][CH:9]1[CH2:14][CH2:13][CH2:12][CH2:11][O:10]1)#[C-:34]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 113606702-(6-Bromo-2-methyl-2-p-tolylhexyloxy)-tetrahydropyran

Product 1

HCID 234313592-[7-Isocyano-2,12-dimethyl-2, 12-di-p-tolyl-13-(tetrahydropyran-2-yloxy)-7-(toluene-4-sulfonyl)-tridecanyloxy]-tetrahydropyranYield 82%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 3283Diethyl EtherSolvent

Procedure

To a solution of 2-(6-bromo-2-methyl-2-p-tolyl-hexyloxy)-tetrahydropyran (21.5 g, 58.27 mmol), tetra-n-butylammonium iodide (2.36 g, 6.41 mmol), and p-toluenesulphonyl-methyl isocyanide (TosMIC, 5.68 g, 29.14 mmol) in anhydrous DMSO (300 mL) and anhydrous diethyl ether (100 mL) was added sodium hydride (60% dispersion in mineral oil, 2.94 g, 73.42 mmol) at rt under N2 atmosphere. The mixture was stirred for 24 h at rt. The reaction mixture was carefully hydrolized with ice-water (500 mL) and extracted with diethyl ether (2×300 mL). The organic layer was washed with brine (2×300 mL), dried over anhydrous MgSO4, and concentrated in vacuo to furnish crude 2-[7-isocyano-2,12-dimethyl-2,12-di-p-tolyl-13-(tetrahydropyran-2-yloxy)-7-(toluene-4-sulfonyl)-tridecanyloxy]-tetrahydropyran (18.44 g) as a brown oil. A solution of this crude intermediate (18 g) in methanol (300 mL), concd. HCl (36 mL), and water (70 mL) was heated to reflux for 3 h. The reaction mixture was poured into CH2Cl2 (250 mL) and ice-water (250 mL). The layers were separated and the aqueous layer was extracted with CH2Cl2 (3×100 mL). The combined organic layers were washed with saturated NaHCO3 solution (3×100 mL) and brine (150 mL), dried over anhydrous MgSO4 and concentrated in vacuo. The resulting crude oil was purified by flash chromatography (silica gel, ethyl acetate/hexanes=20/1, 15/1, 10/1, 5/1, and 1/1) to furnish 1,13-dihydroxy-2,12-dimethyl-2,12-di-p-tolyl-tridecan-7-one (2.72 g, 26.2% over two steps) as a colorless oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm) 7.18 (d, 4H, J=8.1 Hz), 7.12 (d, 4H, J=8.1 Hz), 3.63 (d, J=11.0 Hz, 2H), 3.49 (d, J=1.0 Hz, 2H), 2.31 (s, 6H), 2.26 (t, J=7.8 Hz, 4H), 1.78-1.40 (m, 10H), 1.28 (s, 6H), 1.24-0.82 (m, 4H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm) 211.51, 141.75, 135.64, 129.23, 126.64, 72.54, 43.06, 42.65, 38.28, 24.53, 23.59, 21.66, 20.98. HRMS (LSIMS, nba): Calcd. for C29H43O3 (MH+): 439.3212, found: 439.3222.

Workup

  1. extractionextracted with diethyl ether (2×300 mL)
  2. washThe organic layer was washed with brine (2×300 mL)
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-7edb629d242341579b67be545ad95623
Source dataset
uspto-grants-2004_03
Patent number
US06699910B2

Reaction notes

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