Propanal → HCID 11423661, compound

HRID 2184382Notes

Reaction equation

HRID 2184382 reaction equation
[CH:1](=[O:4])[CH2:2][CH3:3].[CH:5](=[O:10])[CH2:6][CH:7]([CH3:9])[CH3:8].N1CCC[C@H]1C(O)=O>CN(C)C=O.C(OCC)C>[OH:10][C@@H:5]([CH2:6][CH:7]([CH3:9])[CH3:8])[C@H:2]([CH3:3])[CH:1]=[O:4]

Participants

6

Reactant 3

HCID 527PropanalHCID 115523-MethylbutanalHCID 145742L-Proline

Product 1

HCID 11423661HCID 11423661, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 6228DimethylformamideSolvent2×

Procedure

A solution of freshly distilled propionaldehyde (144 μL, 2.0 mmol) in 500 μL dimethylformamide pre-cooled to 4° C. was added slowly over the course of 2.5 h to a stirring suspension of isovaleraldehyde (107 μL, 1.0 mmol), L-proline (11.5 mg, 0.10 mmol) and 500 μL dimethylformamide at 4° C. After 16 h, 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 of 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 88% yield (126 mg, 0.88 mmol), 97% ee and 3:1 anti:syn. IR (film) 3419, 2958, 2935, 2872, 1719,1466, 1368, 1152, 1098, 1062,1025, 976.5 cm−1; 1H NMR (300 MHz, CDCl3) δ9.75 (d, J=1.5 Hz, 1H, CHO); 3.89 (ddd, 1H, J=9.9, 6.6, 2.7 Hz, 1H, CHOH); 2.44 (m, 1H, CHCH3); 1.83 (m, 1H, CH(CH3)2); 1.47 (m, 1H, CH2); 1.26 (m, 1H, CH2); 1.14 (d, 3H, J=7.2 Hz, CH3CHCHO); 0.97 (d, 3H, J=5.1 Hz, (CH3)2CH); 0.92 (d, 3H, J=6.6 Hz, (CH3)2CH); 13C NMR (75 MHz, CDCl3) δ205.5, 70.9, 52.8, 44.0, 34.5, 24.1, 21.8, 11.1; HRMS (CI) exact mass calcd for [M +H]+ (C8H17O2) requires m/z 145.1228, found m/z 145.1225; [α]D=−33.6 (c=1.0, CHCl3). The product ratios were determined by GLC analysis of the acetal derived from 2,2-dimethylpropane-1,3-diol (obtained by the method of Yamamoto, supra) using a Bodman Chiraldex β-DM (30 m×0.25 mm) column (100° C. isotherm, 23 psi); (2S, 3S) anti isomer tr=50.8 min, (2R, 3R) anti isomer tr=53.2 min, (2R, 3S) and (2S, 3R) syn isomers tr=45.5 min.

Workup

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

Sources & evidence

ORD record
ord-bd56e7b55f154071b87e7466617a48f5
Source dataset
uspto-grants-2005_05
Patent number
US06900357B2

Reaction notes

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