Reaction #1810814

Reaction equation

3-Dimethylaminopropyl-3-ethylcarbodiimide hydrochloride

proline methyl ester hydrochloride

55

N-Allyl-N-benzyloxycarbonylglycine

triethylamine

→

dipeptide

N-Allyl-N-benzyloxycarbonylglycyl-L-proline methyl ester

Solvents

dichloromethane

Conditions

Workup

1. 1
   Washwashed with 2M aqueous hydrochloric acid and saturated aqueous sodium hydrogen carbonate
2. 2
   Dryingdried (MgSO4)
3. 3
   Otherthe solvent removed
4. 4
   Otherto yield an oil which
5. 5
   Otherwas purified by chromatography (silica gel, hexanes:ethyl acetate, 2:1, 1:1)

Procedure

1-(3-Dimethylaminopropyl-3-ethylcarbodiimide hydrochloride (EDCI) (0.453 g, 2.36 mmol) was added to a solution of proline methyl ester hydrochloride 30 (0.356 g, 2.15 mmol), acid 55 (0.590 mmol, 2.35 mmol) and triethylamine (0.481 g, 4.73 mmol) in dichloromethane (20 cm3) at 0° C. The resultant solution was stirred for 19 h, washed with 2M aqueous hydrochloric acid and saturated aqueous sodium hydrogen carbonate, dried (MgSO4) and the solvent removed to yield an oil which was purified by chromatography (silica gel, hexanes:ethyl acetate, 2:1, 1:1) to afford protected dipeptide 56 (0.508 g, 66%) as a colourless oil. Dipeptide 56 was shown to be a 76:24 trans:cis mixture of conformers by 13C NMR analysis (the ratio was estimated by integration of signals at δ 22.0 and 24.5, 24.7, assigned to the Proγ-C atoms of the minor and major conformers respectively). In addition, restricted rotation about the GlyN—CO carbamate bond was also observed resulting in a further 1:1 mixture of conformers: [α]D −54.6 (c 1.17 in CH2Cl2); δH (400 MHz; CDCl3; Me4Si) 1.81-2.14 (4H, m, Proβ-H2, Proγ-H2), 3.29-3.58 (2H, m, Proδ-H2), 3.64, 3.66, 3.69* (3H, s, OCH3), 3.84-4.20 [4H, m, CH2(allyl), Glyα-H2], 4.40-4.48 (1H, m, Proα-H), 5.07-5.17 (4H, m, OCH2Ph, ═CH2), 5.69-5.81 (1H, m, C(H)═CH2) and 7.24-7.30 (m, 5H, Ph); δC (100 MHz; CDCl3) 22.0* (CH2, Proγ-C), 24.62, 24.73 (CH2, Proγ-C), 28.66, 28.73 (CH2, Proβ-C), 31.1,* 31.3* (CH2, Proβ-C), 45.93, 45.98 (CH2, Proδ-C), 46.5* (CH2, Proδ-C), 47.5, 48.0 (CH2, Glyα-C), 50.0, 50.6 [CH2, CH2(allyl)], 50.0,* 50.6* [CH2, CH2(allyl)], 52.0, (CH3, OCH3), 52.31,* 52.5* (CH3, OCH3), 58.4,* 58.5* (CH, Proα-C), 58.8 (CH, Proα-C), 67.2, 67.3 (CH2, OCH2Ph), 117.0, 117.5 (CH2, ═CH2), 127.5, 127.7, 127.8, 128.3, (CH, Ph), 133.2, 133.4 (CH, C(H)═CH2) 136.4, 136.5 (quat., Ph), 155.8, 156.3, (quat., NCO2), 167.1 (quat., Gly-CO), 167.4,* 167.5* (quat., Gly-CO). 172.0,* 172.2* (quat., Pro-CO) and 172.3, 172.4 (quat., Pro-CO); m/z (EI+) 360.1676 (M+. C19H24N2O5 requires 360.1685).

Source