Pyridine → 4-[5-Allyloxycarbonylamino-4-(2-hydroxymethyl-pyrrolidine-1-carbonyl)-2-methoxy-phenoxy]-butyric acid methyl ester

HRID 476399Notes

Reaction equation

HRID 476399 reaction equation
[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[C:12]([NH2:14])[C:11]([C:15]([N:17]2[CH2:21][CH2:20][CH2:19][CH:18]2[CH2:22][OH:23])=[O:16])=[CH:10][C:9]=1[O:24][CH3:25].N1C=CC=CC=1.Cl[C:34]([O:36][CH2:37][CH:38]=[CH2:39])=[O:35]>C(Cl)Cl>[CH3:1][O:2][C:3](=[O:26])[CH2:4][CH2:5][CH2:6][O:7][C:8]1[CH:13]=[C:12]([NH:14][C:34]([O:36][CH2:37][CH:38]=[CH2:39])=[O:35])[C:11]([C:15]([N:17]2[CH2:21][CH2:20][CH2:19][CH:18]2[CH2:22][OH:23])=[O:16])=[CH:10][C:9]=1[O:24][CH3:25]

Participants

5

Reactant 3

HCID 1049PyridineHCID 18052Allyl chloroformateHCID 688432654-[5-Amino-4-(2-hydroxymethyl-pyrrolidine-1-carbonyl)-2-methoxy-phenoxy]-butyric acid methyl ester

Product 1

HCID 688450094-[5-Allyloxycarbonylamino-4-(2-hydroxymethyl-pyrrolidine-1-carbonyl)-2-methoxy-phenoxy]-butyric acid methyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

A batch of the amine 15 (22.5 g, 61.5 mmol) was dissolved in anhydrous DCM (300 mL) in the presence of anhydrous pyridine (10.9 mL, 134 mmol) at 0° C. Allyl chloroformate (7.17 mL, 67.5 mmol) diluted in anhydrous DCM (200 mL) was added dropwise at 0° C. The resulting solution was allowed to stir overnight at room temperature. It was then washed with cold 1N aqueous HCl (200 ml), water (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL). The solution was then dried (MgSO4), and the solvent was removed in vacuo to provide 16, slightly contaminated by the product of diacylation (27 g, quantitative yield). A sample was columned (EtOAc/Hexane) to provide the analytical data. 1H NMR (CDCl3) δ 8.78 (1H, bs), 7.75 (1H, s), 6.82 (1H, s), 5.97 (1H, m), 5.38-5.34 (1H, dd, J=1.5, 17.2 Hz), 5.27-5.24 (1H, dd, J=1.3, 10.4 Hz, 1H), 4.63 (2H, m), 4.40 (2H, bs), 4.11 (2H, t, J=6.3 Hz), 3.82 (3H, s), 3.69 (4H, m), 3.61-3.49 (2H, m), 2.54 (2H, t, J=7.4 Hz), 2.18 (2H, p, J=6.7 Hz), 1.92-1.70 (4H, m); 13C NMR (CDCl3) δ 173.4, 170.9, 153.6, 150.5, 144.0, 132.5, 132.0, 118.1, 115.4, 111.6, 105.6, 67.7, 66.6, 65.8, 61.1, 60.4, 56.6, 51.7, 30.5, 28.3, 25.1, 24.3; MS (FAB+) m/z 50 (451, M+H); IR (golden gate) vmax 2949, 2359, 1728, 1596, 1521, 1433, 1202, 1173, 1119, 998, 844, 652 cm−1; [α]26D=−67° (c=0.45, CHCl3).

Workup

  1. additionwas added dropwise at 0° C
  2. washIt was then washed with cold 1N aqueous HCl (200 ml), water (200 mL), saturated aqueous NaHCO3 (200 mL), and brine (200 mL)
  3. dry with materialThe solution was then dried (MgSO4)
  4. customthe solvent was removed in vacuo

Sources & evidence

ORD record
ord-b758a8f044294c8c92421bd7e3d2b59f
Source dataset
uspto-grants-2014_01
Patent number
US08637664B2

Reaction notes

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