Methyl iodide → 2-[(R)-3,7-dimethyloctanoxy]-tetrahydro-2H-pyran

HRID 1390184Notes

Reaction equation

HRID 1390184 reaction equation
CI.[Mg].Br[CH2:5][C@@H:6]([CH3:16])[CH2:7][CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1.[CH3:17][CH:18]([CH3:22])[CH2:19][CH2:20]O.C1(C)C=CC(S([O-])(=O)=O)=CC=1>O1CCCC1>[CH3:16][C@H:6]([CH2:5][CH2:20][CH2:19][CH:18]([CH3:22])[CH3:17])[CH2:7][CH2:8][O:9][CH:10]1[CH2:15][CH2:14][CH2:13][CH2:12][O:11]1

Participants

6

Reactant 4

HCID 6328Methyl iodideHCID 5462224MagnesiumHCID 13937367HCID 13937367, compound3×HCID 867362793-Methyl-1-butanol p-toluenesulphonate

Product 1

HCID 536988862-[(R)-3,7-dimethyloctanoxy]-tetrahydro-2H-pyran

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4.7 g (0.202 mol) of magnesium shavings in a 3-necked flask under an argon atmosphere and provided with a calcium chloride tube are activated by addition of 2.0 ml of methyl iodide. After 5 minutes, the methyl iodide is removed and the magnesium washed several times with absolute tetrahydrofuran. To the activated magnesium is added dropwise a solution of 44 g (0.175 mol) of 2-[(S)-4-bromo-3-methylbutoxy]-tetrahydro-2H-pyran in 50 ml of absolute tetrahydrofuran at such a rate that the solvent just boils. Where the Grignard reaction does not start itself, it is warmed to 85° with the oil bath. After completed addition of 2-[(S)-4-bromo-3-methylbutoxy]-tetrahydro-2H-pyran, the mixture is stirred at 85° for so long (0-15 min.) until only traces of 2-[(S)-4-bromo-3-methylbutoxy]-tetrahydro-2H-pyran are still present in accordance with gas-chromatographical analysis. The solution obtained is cooled to -78° and treated dropwise with 21.2 g (0.0875 mol) of 3-methyl-1-butanol-p-toluenesulphonate followed by 3.6 ml of a 0.1 molar solution of Li2CuCl4 in absolute tetrahydrofuran. This reaction mixture is stirred at -78° during 10 min. then at 0° for 2 hours and subsequently at room temperature for a further 14 hours. For the working up of the 2-[(R)-3,7-dimethyloctanoxy]-tetrahydro-2H-pyran obtained the mixture is poured on to ice and brought to pH 5-6 with 2-N sulphuric acid. By three-fold extraction with ether and removal of the solvent on the rotary evaporator there is obtained a mixture of (R)-3,7-dimethyl-1-octanol and 2-[(R)-3,7-dimethyloctanoxy]-tetrahydro-2H-pyran. This mixture is treated portionwise in 100 ml of methanol at 0° with a total of 100 ml of 7-N aqueous hydrochloric acid. After 2-hours stirring at room temperature, the mixture is neutralised with dilute aqueous caustic soda and extracted with ether. After chromatography on silicagel, deactivated with 0.5% ammonia, with pentane/ether (4:1), there are obtained 10.6 g (76% based on 3-methyl-1-butanol-p-toluenesulphonate employed) of pure (R)-3,7-dimethyl-1-octanol. B.p. 58°-59°/0.05 Torr; [α]D20 = +4.0 (c = 1.03, CHCl3).

Workup

  1. customthe methyl iodide is removed
  2. customWhere the Grignard reaction
  3. temperatureis warmed to 85° with the oil bath
  4. customThe solution obtained
  5. temperatureis cooled to -78°
  6. waitat 0° for 2 hours
  7. waitsubsequently at room temperature for a further 14 hours

Sources & evidence

ORD record
ord-7bb4ca47d4b0485baaba1d574eb48d78
Source dataset
uspto-grants-1979_02
Patent number
US04138289

Reaction notes

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