Methanol → HCID 11243945, compound

HRID 873281Notes

Reaction equation

HRID 873281 reaction equation
[CH2:1]([O:3][C:4](=[O:25])[C:5]([CH3:24])([CH3:23])[CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([N+]#[C-])S(C1C=CC(C)=CC=1)(=O)=O)[CH3:2].[H-].[Na+].[CH3:28][OH:29].[OH2:30]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.CS(C)=O.OS(O)(=O)=O>[OH:29][CH2:28][C:5]([CH3:23])([CH3:4])[CH2:6][CH2:7][CH2:8][C:10](=[O:30])[CH2:9][CH2:8][CH2:7][CH2:6][C:5]([CH3:23])([CH3:24])[C:4]([O:3][CH2:1][CH3:2])=[O:25]

Participants

8

Reactant 4

HCID 887MethanolHCID 962WaterHCID 24758Sodium hydrideHCID 11268576Ethyl 7-isocyano-2,2-dimethyl-7-[(4-methylphenyl)sulfonyl]heptanoate

Product 1

HCID 11243945HCID 11243945, compoundYield 60%

Reagents, catalysts & solvents 3

HCID 67553Tetrabutylammonium IodideCatalystHCID 679Dimethyl SulfoxideSolventHCID 1118Sulfuric AcidSolvent

Procedure

Under nitrogen atmosphere, to a solution of 220 (1.72 g, 4.68 mmol), tetrabutylammonium iodide (0.17 g, 0.46 mmol) and 207a (1.45 g, 5.19 mmol) in anhydrous DMSO (20 mL) was added NaH (60% w/w in mineral oil, 0.19 g, 4.75 mmol), while keeping the internal temperature between 10 and 15° C. The reaction mixture was stirred for 20 h at room temperature and then carefully hydrolyzed with ice-water (100 mL). The mixture was extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude intermediate (3.50 g) as brown oil. A solution of this intermediate in 48% H2SO4 (6 mL) and methanol (12 mL) was stirred for 100 min at room temperature. The mixture was diluted with water (50 mL) and extracted with CH2Cl2 (3×15 mL). The combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL), dried over anhydrous MgSO4, and concentrated in vacuo to obtain the crude product (2.70 g) as yellow oil. A portion of the crude product (2.50 g) was subjected to column chromatography (silica gel; hexanes/ethyl acetate=80/20, then 75/25) to give 221 (0.82 g, 60%) as a pale yellow oil. 1H NMR (CDCl3): δ 4.14-4.03 (m, 2H), 3.31 (br. s, 2H), 2.42 (br., 1H), 2.39 (m, 4H), 1.54-1.48 (m, 6H), 1.24-1.18 (m, 7H), 1.14 (s, 6 μl), 0.86 (s, 6H). 13C NMR (CDCl3): δ 211.7, 178.0, 71.2, 60.3, 43.2, 42.7, 42.1, 40.4, 37.9, 35.1, 25.2, 24.6, 24.2, 24.1, 18.0, 14.3. HRMS (LSIMS, gly): Calcd for C18H35O4 (MH+): 315.2535, found: 315.2541.

Workup

  1. customthe internal temperature between 10 and 15° C
  2. extractionThe mixture was extracted with CH2Cl2 (3×15 mL)
  3. washThe combined organic layers were washed with water (40 mL) and saturated aqueous NaCl solution (2×20 mL)
  4. dry with materialdried over anhydrous MgSO4
  5. concentrationconcentrated in vacuo
  6. customto obtain the crude intermediate (3.50 g) as brown oil
  7. extractionextracted with CH2Cl2 (3×15 mL)
  8. washThe combined organic layers were washed with water (100 mL) and saturated aqueous NaCl solution (100 mL)
  9. dry with materialdried over anhydrous MgSO4
  10. concentrationconcentrated in vacuo
  11. customto obtain the crude product (2.70 g) as yellow oil

Sources & evidence

ORD record
ord-446e27272a194d889c1da720dd3cc99e
Source dataset
uspto-grants-2015_03
Patent number
US08975300B2

Reaction notes

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