Triethylamine → 5-Allyl-1-(2-tert-butoxycarbonylamino-pent-4-enoyl)-pyrrolidine-2-carboxylic acid methyl ester

HRID 1824417Notes

Reaction equation

HRID 1824417 reaction equation
Cl.[CH3:2][O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH:8](OCC=C)[NH:7]1)=[O:5].C(N(CC)CC)C.[C:22]([O:26][C:27]([NH:29][CH:30]([CH2:34][CH:35]=[CH2:36])[C:31]([OH:33])=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].[CH:37]1(N=C=NC2CCCCC2)[CH2:42]CCC[CH2:38]1>C(Cl)Cl.CN(C)C1C=CN=CC=1>[CH3:2][O:3][C:4]([CH:6]1[CH2:10][CH2:9][CH:8]([CH2:42][CH:37]=[CH2:38])[N:7]1[C:31](=[O:33])[CH:30]([NH:29][C:27]([O:26][C:22]([CH3:23])([CH3:24])[CH3:25])=[O:28])[CH2:34][CH:35]=[CH2:36])=[O:5]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 51661192-{[(Tert-butoxy)carbonyl]amino}pent-4-enoic acidHCID 695844965-Allyloxy-pyrrolidine-2-carboxylic acid methyl ester hydrochloride

Product 1

HCID 235714265-Allyl-1-(2-tert-butoxycarbonylamino-pent-4-enoyl)-pyrrolidine-2-carboxylic acid methyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To a solution of 5-allyloxy-pyrrolidine-2-carboxylic acid methyl ester hydrochloride, 5, (17.82 g, 86.6 mmol) and triethylamine (36 mL, 260 mmol) in CH2Cl2 (500 mL), 2-tert-butoxycarbonylamino-pent-4-enoic acid (41.1 g, 191 mmol), 1,3-dicyclohexylcarbodiimide (46.4 g, 225 mmol), and 4-dimethylaminopyridine (21.1 g, 173 mmol) are added. Once consumption of the starting material is complete, the precipitate that forms is filtered from the reaction mixture. The CH2Cl2 is reduced in vacuo and residue which remains is diluted with ether (500 mL). A white precipitate forms which is collected by filtration. The solvent is then removed and the resulting residue dissolved in ethyl acetate (250 mL) then further diluted with hexanes (250 mL). A white precipitate again forms and is removed. The solution which remains is concentrate in vacuo and the residue purified over silica (hexanes/ethyl acetate 80:20) to afford 27.69 g (87% yield) of the desired product as a slightly yellow oil. 1H-NMR (300 MHz, CDCl3): δ 5.91–5.74 (m, 2H), 5.22–5.01 (m, 5H), 4.55–4.40 (m, 3H), 3.81–3.74 (m, 3H), 2.60–1.90 (m, 4H), 1.45 (s, 9H); 13C-NMR (75.5 MHz, CDCl3): δ 183.85, 172.92, 172.52, 171.69, 155.58, 135.05, 134.27, 133.45, 118.63, 117.43, 80.00, 60.00, 59.58, 58.47, 52.41, 52.41, 52.10, 51.20, 39.69, 38.09, 29.82, 28.54, 27.11; MS (ESI): m/e=367.21 (M+H).

Workup

  1. customOnce consumption of the starting material
  2. filtrationthe precipitate that forms is filtered from the reaction mixture
  3. additionremains is diluted with ether (500 mL)
  4. filtrationA white precipitate forms which is collected by filtration
  5. customThe solvent is then removed
  6. dissolutionthe resulting residue dissolved in ethyl acetate (250 mL)
  7. additionthen further diluted with hexanes (250 mL)
  8. customis removed
  9. concentrationThe solution which remains is concentrate in vacuo
  10. customthe residue purified over silica (hexanes/ethyl acetate 80:20)

Sources & evidence

ORD record
ord-bb346cd6f14747b9803dc4d3b4477b83
Source dataset
uspto-grants-2006_05
Patent number
US07041696B2

Reaction notes

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