Hydroxylamine → Cyclohexanemethanol, alpha-ethyl-, 1-acetate

HRID 279405Notes

Reaction equation

HRID 279405 reaction equation
NO.[CH:3]1([CH:9]=[O:10])[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1.C([Zn][CH2:14][CH3:15])C.[C:16](OC(=O)C)(=[O:18])[CH3:17]>CCCCCC.CCOCC.C1(C)C=CC=CC=1>[C:16]([O:10][CH:9]([CH:3]1[CH2:8][CH2:7][CH2:6][CH2:5][CH2:4]1)[CH2:14][CH3:15])(=[O:18])[CH3:17]

Participants

8

Reactant 4

HCID 787HydroxylamineHCID 7918Acetic AnhydrideHCID 16275CyclohexanecarboxaldehydeHCID 178418750HCID 178418750, compound

Product 1

HCID 102753Cyclohexanemethanol, alpha-ethyl-, 1-acetateYield 81%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 3283Diethyl EtherSolventHCID 8058HexaneSolvent

Procedure

To a vial containing aminoalcohol 1 (0.05 g, 0.17 mmol) prepared as in Example 1 was added a solution containing freshly distilled cyclohexane-carboxaldehyde (0.34 g, 3.0 mmol), toluene (3.0 mL), and 1 M diethylzinc in hexane (6.0 mL). After 3 days at room temperature, acetic anhydride (1.2 mL, 13 mmol) was added. After 2 additional days, the mixture was diluted in ether (50 mL) and the reaction was quenched by dropwise addition of half-saturated aqueous ammonium chloride (50 mL). The ether layer was separated and the aqueous layer was further extracted with ether (2×50 mL). The combined ether layers were dried over magnesium sulfate whereupon the solvent was removed at reduced pressure. The residue was purified by flash chromatography on 220-400 mesh silica with 90% hexane and 10% ethyl acetate as eluant. The product (+)-1-cyclohexylpropyl acetate (0.45 g, 81%) was isolated as a colorless liquid by distillation at reduced pressure. Anal. for C11H20O2. Calcd: C, 71.70; H, 10.94; found: C, 71.41; H, 10.69. 1H NMR (CDCl3/TMS): δ 0.85 (t, 3 H, J=7), 0.98 (m, 2 H), 1.08-1.26 (m, 3 H), 1.42-1.75 (m, 8 H), 2.04 (s, 3 H), 4.66 (m, 1 H). 13C NMR (CDCl3/TMS): δ 9.80, 21.14, 24.11, 26.21, 26.58, 28.22, 40.90, 79.25, 171.09. [α]D25=+27.6, c=2.06 g/100 mL chloroform. Chiral capillary gas chromatographic analysis at 120° C. on Cyclodex B stationary phase (J & W Scientific) indicated that the enantiomeric excess of the product was 97%.

Workup

  1. additionTo a vial containing
  2. additionwas added a solution
  3. customthe reaction was quenched by dropwise addition of half-saturated aqueous ammonium chloride (50 mL)
  4. customThe ether layer was separated
  5. extractionthe aqueous layer was further extracted with ether (2×50 mL)
  6. dry with materialThe combined ether layers were dried over magnesium sulfate whereupon the solvent
  7. customwas removed at reduced pressure
  8. customThe residue was purified by flash chromatography on 220-400 mesh silica with 90% hexane and 10% ethyl acetate as eluant

Sources & evidence

ORD record
ord-5cbaa3aaae9e4d219c9116160a66e07a
Source dataset
uspto-grants-2002_03
Patent number
US06362344B1

Reaction notes

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