Triethylamine → HCID 57558965, compound

HRID 907484Notes

Reaction equation

HRID 907484 reaction equation
Cl.CN(C)CCCN=C=NCC.Cl.[CH3:14][O:15][C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][NH:18]1.[CH2:23]([N:26]([C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32])[CH2:27][C:28](O)=[O:29])[CH:24]=[CH2:25].C(N(CC)CC)C>ClCCl>[CH3:14][O:15][C:16](=[O:22])[C@@H:17]1[CH2:21][CH2:20][CH2:19][N:18]1[C:28](=[O:29])[CH2:27][N:26]([CH2:23][CH:24]=[CH2:25])[C:31]([O:33][CH2:34][C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1)=[O:32]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2733200methyl L-prolinate hydrochlorideHCID 15092217N-[(Phenylmethoxy)carbonyl]-N-2-propen-1-ylglycine

Product 1

HCID 57558965HCID 57558965, compoundYield 238.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

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 δ22.0 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, ProβH2, 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, ProδC), 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).

Workup

  1. washwashed with 2M aqueous hydrochloric acid and saturated aqueous sodium hydrogen carbonate
  2. dry with materialdried (MgSO4)
  3. customthe solvent removed
  4. customto yield an oil which
  5. customwas purified by chromatography (silica gel, hexanes:ethyl acetate, 2:1, 1:1)

Sources & evidence

ORD record
ord-307e2cb1b1984e158cd6af0bf83f643c
Source dataset
uspto-grants-2011_09
Patent number
US08013170B2

Reaction notes

Loading…