Sodium hydride → 2-[8-Isocyano-2,2,14,14-tetramethyl-15-(tetrahydropyran-2-yloxy)-8-(toluene-4-sulfonyl)-pentadecyloxy]-tetrahydropyran

HRID 2057181Notes

Reaction equation

HRID 2057181 reaction equation
Br[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([CH3:17])([CH3:16])[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1.[C:18]1([CH3:30])[CH:23]=[CH:22][C:21]([S:24]([CH2:27][N+:28]#[C-:29])(=[O:26])=[O:25])=[CH:20][CH:19]=1.[H-].[Na+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O>[N+:28]([C:27]([S:24]([C:21]1[CH:20]=[CH:19][C:18]([CH3:30])=[CH:23][CH:22]=1)(=[O:25])=[O:26])([CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([CH3:16])([CH3:17])[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6][C:7]([CH3:17])([CH3:16])[CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1)#[C-:29]

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 161915Tosylmethyl isocyanideHCID 112090012-(7-Bromo-2,2-dimethylheptyloxy)-tetrahydropyran

Product 1

HCID 865966182-[8-Isocyano-2,2,14,14-tetramethyl-15-(tetrahydropyran-2-yloxy)-8-(toluene-4-sulfonyl)-pentadecyloxy]-tetrahydropyranYield 220.9%

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolvent

Procedure

Under nitrogen atmosphere, to a solution of 2-(7-bromo-2,2-dimethylheptyloxy)-tetrahydropyran (26.0 g, 39.4 mmol), tetra-n-butylammonium iodide (3.0 g, 8.1 mmol) and p-toluenesulfonyl methyl isocyanide (7.80 g, 39.4 mmol) in anhydrous DMSO (200 mL) was added sodium hydride (3.80 g, 20.5 mmol, 60% dispersion in mineral oil) in portions at 5-10° C. The reaction mixture was stirred at room temperature for 20 h and quenched with ice-water (400 mL). The product was extracted with diethyl ether (3□100 mL). The combined organic layers were washed with water (200 mL) and saturated sodium chloride solution (2×200 mL), dried over MgSO4, and concentrated in vacuo to get crude 2-[8-isocyano-2,2,14,14-tetramethyl-15-(tetrahydropyran-2-yloxy)-8-(toluene-4-sulfonyl)-pentadecyloxy]-tetrahydropyran (28.2 g) as an orange oil, which was used without purification. A solution of this crude product (28.0 g) and 48% sulfuric acid (46 g, from 12 mL of concentrated sulfuric acid and 24 mL of water) in methanol (115 mL) was stirred for 80 min at room temperature. The solution was diluted with ice-water (120 mL). The aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic layers were washed with saturated Na2CO3 solution (2×150 mL) and saturated NaCl solution (150 mL). The organic solution was dried over MgSO4 and concentrated in vacuo. The residue was purified by column chromatography (silica gel, hexanes:ethyl acetate=2:1) to give 8-oxo-2,2,14,14-tetramethylpentadecane-1,15-diol (9.97 g, 80% over two steps) as a colorless oil. 1H NMR (300 MHz, CDCl3/TMS): δ (ppm): 3.30 (s, 4H), 2.39 (t, 4H, J=7.2 Hz), 2.07 (br. s, 2H), 1.60-1.55 (m, 4H), 1.28-1.17 (m, 12H), 0.85 (s, 12H). 13C NMR (75 MHz, CDCl3/TMS): δ (ppm): 212.0, 72.0, 43.0, 38.6, 35.2, 30.3, 24.0, 23.8. HRMS (LSIMS, gly): Calcd. for C19H39O3 (MH+): 315.2899, found: 315.2886. HPLC: 94.7% purity.

Workup

  1. customquenched with ice-water (400 mL)
  2. extractionThe product was extracted with diethyl ether (3□100 mL)
  3. washThe combined organic layers were washed with water (200 mL) and saturated sodium chloride solution (2×200 mL)
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-736acb0030ce4edb94f749238255c24d
Source dataset
uspto-grants-2008_02
Patent number
US07335799B2

Reaction notes

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