Potassium bisulfate → (Rs)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanal

HRID 394935Notes

Reaction equation

HRID 394935 reaction equation
CON(C)[C:4](=[O:23])[CH:5]([C:11]1[CH:12]=[C:13]2[C:18](=[CH:19][CH:20]=1)[S:17][CH2:16][CH2:15][C:14]2([CH3:22])[CH3:21])[CH2:6][CH2:7][CH2:8][CH2:9][CH3:10].[H-].[Al+3].[Li+].[H-].[H-].[H-].OS([O-])(=O)=O.[K+]>C1COCC1>[CH3:21][C:14]1([CH3:22])[C:13]2[C:18](=[CH:19][CH:20]=[C:11]([CH:5]([CH2:6][CH2:7][CH2:8][CH2:9][CH3:10])[CH:4]=[O:23])[CH:12]=2)[S:17][CH2:16][CH2:15]1

Participants

5

Reactant 3

HCID 516920Potassium bisulfateHCID 21226445Aluminium lithium hydrideHCID 87949148(Rs)-n-methoxy-n-methyl-2-(4,4-dimethyl-thiochroman-6-yl)-heptanoic amide

Product 1

HCID 18177929(Rs)-2-(4,4-dimethyl-thiochroman-6-yl)-heptanalYield 86%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-40 °C

Procedure

0.49 g of (RS)-N-methoxy-N-methyl-2-(4,4-dimethyl-thiochroman-6-yl)-heptanoic amide was dissolved in 5 ml THF and treated with 1.6 ml of 1M lithium aluminium hydride solution in THF at −40° C. The mixture was stirred at −40° C. for 30 min. then allowed to warm to room temperature over 1.5 hour. The mixture was cooled back to −40° C. and 3.5 ml of 20% aqueous KHSO4 solution was added over 5 min. The mixture was stirred at room temperature for one hour. The reaction mixture was partitioned in 100 ml ethyl acetate/50 ml water and the phases were separated. The aqueous phase was extracted with three portions of 15 ml of ethyl acetate. The combined organic extracts were washed with one portion of 25 ml of water, one portion of 25 ml of 1 N hydrochloric acid, one portion of 25 ml of saturated aqueous sodium bicarbonate solution and one portion of 25 ml of saturated aqueous sodium chloride solution. The organic phase was dried over MgSO4 and concentrated in vacuo, giving 0.35 g of the titled compound which was used without purification. 1H NMR (CDCl3): 9.61 (d, J=2.2 Hz, 1H), 7.13 (d, J=2.0 Hz, 1H), 7.08 (d, J=8.1 Hz, 1H), 6.86 (dd, J=8.1, 2.0 Hz, 1H), 3.45-3.35 (m, 1H), 3.05-3.00 (m, 2H), 2.10-1.90 (m, 3H), 1.70-1.50 (m, 1H), 1.32 (s, 6H), 1.35-1.20 (m, 6H), 0.86 (br.t, J=6.7 Hz, 3H).

Workup

  1. temperatureto warm to room temperature over 1.5 hour
  2. temperatureThe mixture was cooled back to −40° C.
  3. stirringThe mixture was stirred at room temperature for one hour
  4. customThe reaction mixture was partitioned in 100 ml ethyl acetate/50 ml water
  5. customthe phases were separated
  6. extractionThe aqueous phase was extracted with three portions of 15 ml of ethyl acetate
  7. washThe combined organic extracts were washed with one portion of 25 ml of water, one portion of 25 ml of 1 N hydrochloric acid, one portion of 25 ml of saturated aqueous sodium bicarbonate solution and one portion of 25 ml of saturated aqueous sodium chloride solution
  8. dry with materialThe organic phase was dried over MgSO4
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-1270035cc2094f1780962581769b20c0
Source dataset
uspto-grants-2003_08
Patent number
US06603012B2

Reaction notes

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