1-Boc-3-pyrrolidinecarbaldehyde

Colorless to light yellow oil

1 kg of N-Boc-pyrrolidine-3-methanol was dissolved in 5 liters of DMSO, Room temperature by adding manganese dioxide 2.14kg, Room temperature reaction for about 24 hours, Reaction is completed, filter, Spin dry solvent, N-Boc-pyrrolidine-3-carbaldehyde (920 g) was distilled off under reduced pressure, Yield 93percent.To a solution of oxalyl chloride (3.86 mL, 44.2 mmol) in CH2C12 (80mL) at-78 C under N2 was added a solution of dimethyl sulfoxide (6.28 mL, 88.5 mmol) inCH2Cl2 (20 mL). After 10 minutes, a solution of 3-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (8.09 g, 40.2 mmol) inCH2Cl2 (30 mL) was added over 15 minutes. After a further 30 minutes, triethylamine (28. 0 mL, 201 mmol) was added, and the reaction mixture was stirred for 1 hour at-78 C then 1 hour at room temperature. The reaction mixture was washed twice with water then with brine, dried (Na2SO4) and concentrated under reduced pressure. The crude product was purified by column chromatography (hexanes: ethyl acetate 9: 1 to 1: 1) to give the titlecompound (6. 98 g, 87percent). lH NMRa (CDCl3) 9.69 (d, J 1.7 Hz, 1H), 3.26-3. 80 (m, 4H), 3.03 (m, 1H), 2.02-2. 29 (m, 2H), 1.46 (s, 9H).To a solution of oxalyl chloride (3.86mL, 44.2 mmol) inCH2Cl2(80mL)at-78 C under N2 was added a solution of dimethyl sulfoxide (6.28mL, 88. 5 mmol) in CH2C12 (20 mL). After 10 minutes, a solution of 3-hydroxymethyl-pyrrolidine-1-carboxylic acid tert-butyl ester (8.09 g, 40.2 mmol) inCH2C12 (30mL) was added over 15 minutes. After a further 30 minutes, triethylamine (28.0mL, 201 mmol) was added, and the reaction mixture was stirred for 1 hour at-78 C then 1 hour at room temperature. The reaction mixture was washed twice with water then with brine, dried(Na2S04) and concentrated under reduced pressure. The crude product was purified by column chromatography (hexanes: ethyl acetate 9: 1 to 1: 1) to give the titlecompound (6.98 g, 87percent). 1H NMR No.(CDCl3) 9.69 (d, J 1.7 Hz, 1H), 3.26-3. 80 (m, 4H), 3.03 (m, 1H), 2.02-2. 29 (m, 2H), 1.46 (s, 9H).General procedure: To a solution of alcohol in CH2Cl2 (0.17M) was added Dess-Martin Periodinane (1.5 equiv) at rt. To the stirred suspension wasthen slowly added H2O (1.1 equiv) using an automatic pipette after which the suspension turned completely white. Stirring wascontinued for 1 h followed by the addition of Et2O (0.02M w.r.t. the alcohol) and the resulting suspension was gentlyconcentrated in vacuo to a few mL after which Et2O was added. The ethereal solution was washed with a 1:1 mixture of sat. aq.NaHCO3 and 10percent Na2S2O3 until the phases became clear. The aqueous phase was back-extracted with Et2O and the combinedethereal phases were dried over MgSO4, filtered and concentrated in vacuo to provide the crude aldehyde that was purified bysilica gel chromatography to provide 1a-h.

Molecular Weight:199.25
XLogP3:0.7
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:199.12084340
Monoisotopic Mass:199.12084340
Topological Polar Surface Area:46.6
Heavy Atom Count:14
Complexity:232
Undefined Atom Stereocenter Count:1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes