Propanal → HCID 11286714, compound

HRID 1983432Notes

Reaction equation

HRID 1983432 reaction equation
[CH:1](=[O:4])[CH2:2][CH3:3].[CH:5]1([CH:11]=[O:12])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1.N1CCC[C@H]1C(O)=O>CN(C)C=O.C(OCC)C>[CH:5]1([C@H:11]([OH:12])[C@H:2]([CH3:3])[CH:1]=[O:4])[CH2:10][CH2:9][CH2:8][CH2:7][CH2:6]1

Participants

6

Reactant 3

HCID 527PropanalHCID 16275CyclohexanecarboxaldehydeHCID 145742L-Proline

Product 1

HCID 11286714HCID 11286714, compoundYield 87%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of freshly distilled propionaldehyde (72 μL, 1.0 mmol) in 500 μL dimethylformamide pre-cooled to 4° C. was added slowly over the course of 20 h to a stirring suspension of cyclohexane carboxaldehyde (242 μL, 2.0 mmol), L-proline (11.5 mg, 0.10 mmol) and 500 μL dimethylformamide at 4° C. After 22 hours, the resulting solution was diluted with diethyl ether and washed successively with water and brine. The combined aqueous layers were back-extracted with 3 portions dichloromethane. The organic layers were combined, dried over anhydrous MgSO4, and concentrated in vacuo. Flash chromatography (20:7 pentane:diethyl ether) afforded the title compound as a clear, colorless oil in 87% yield (148 mg, 0.87 mmol), 99% ee and 93:7 anti: syn. IR (film) 3438, 2928, 2853, 1722, 1450, 1396, 1376, 1314, 1186, 1112, 1063, 975.8, 893.2, 847.5 cm−1; 1H NMR (300 MHz, CDCl3) δ 9.75 (d, 1H, J=2.1 Hz, CHO); 3.53 (dd, 1H, J=7.2, 4.8 Hz, CHOH); 2.58 (m, 1H, CHCH3); 1.8-1.0 (br m, 11H, cyclohexyl); 1.10 (d, 3H, J=7.2 Hz, CH3); 13C NMR (75 MHz, CDCl3) δ 206.1, 77.1, 49.2, 40.7, 30.3, 26.73, 26.69, 26.68, 26.4, 11.4; HRMS (CI) exact mass calcd for [M+H]+(C10H19O2) requires m/z 171.1385, found m/z 171.1386. [α]D=−5.1 (c=1.0, CHCl3). The product ratios were determined by GLC analysis of the corresponding 4-cyclohexyl-2,2,5-trimethyl-[1,3]dioxane (obtained by NaBH4 reduction followed by acetonide protection of the 1,3-diol according to the method of Goto, in Kitamura et al. (1984) J. Am. Chem. Soc. 106:3252) using a Bodman Chiraldex β-DM (30 m×0.25 mm) column (110° C. isotherm, 23 psi); (2S,3R) anti isomer tr=17.8 min, (2R,3R) anti isomer tr=18.7 min, (2R,3R) and (2S,3R) syn isomers tr=21.0, 22.2 min.

Workup

  1. washwashed successively with water and brine
  2. extractionThe combined aqueous layers were back-extracted with 3 portions dichloromethane
  3. dry with materialdried over anhydrous MgSO4
  4. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-f15d317d567f4a9aa731beaa3cd2a890
Source dataset
uspto-grants-2009_06
Patent number
US07541456B2

Reaction notes

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