Glycine methyl ester hydrochloride → Methyl 2-((4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyloxy)carbonylamino)acetate

HRID 2175238Notes

Reaction equation

HRID 2175238 reaction equation
[C:1](=O)([O:34]C1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][C:4]1[CH:9]=[CH:8][C:7]([C:10]2[CH:19]=[CH:18][CH:17]=[C:16]3[C:11]=2[CH2:12][CH2:13][CH2:14][N:15]3[C:20](=[O:33])[CH2:21][CH2:22][CH2:23][O:24][C:25]2[CH:30]=[CH:29][CH:28]=[C:27]([CH3:31])[C:26]=2[CH3:32])=[CH:6][CH:5]=1.Cl.[NH2:46][CH2:47][C:48]([O:50][CH3:51])=[O:49]>C(Cl)Cl>[CH3:32][C:26]1[C:27]([CH3:31])=[CH:28][CH:29]=[CH:30][C:25]=1[O:24][CH2:23][CH2:22][CH2:21][C:20]([N:15]1[C:16]2[C:11](=[C:10]([C:7]3[CH:6]=[CH:5][C:4]([CH2:3][O:2][C:1]([NH:46][CH2:47][C:48]([O:50][CH3:51])=[O:49])=[O:34])=[CH:9][CH:8]=3)[CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:13][CH2:14]1)=[O:33]

Participants

4

Reactant 2

HCID 122755Glycine methyl ester hydrochlorideHCID 867125814-(1-(4-(2,3-Dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyl 4-nitrophenyl carbonate

Product 1

HCID 70982580Methyl 2-((4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyloxy)carbonylamino)acetateYield 63%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(1-(4-(2,3-dimethylphenoxy)butanoyl)-1,2,3,4-tetrahydroquinolin-5-yl)benzyl 4-nitrophenyl carbonate (0.020 g, 0.034 mmol), methyl 2-aminoacetate hydrochloride (5.07 mg, 0.040 mmol) and TEA (9.38 μL, 0.067 mmol) in DCM (0.200 mL) was stirred at room temperature for 16 h. After this time, the reaction mixture was quenched with 1 N NaOH. The organic layer was washed with water and brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The resulting residue was purified by preparative HPLC (PHENOMENEX® Axia Luna column, 5μ, C18, 30×100 mm; 10 min gradient from 75% A:25% B to 0% A:100% B (A=90% H2O/10% MeOH+0.1% TFA); (B=90% MeOH/10% H2O+0.1% TFA); detection at 220 nm) to afford the title compound (11.6 mg, 63% yield) as a clear colorless oil. LCMS, [M+H]+=545.2. 1H NMR (400 MHz, MeOD) δ 7.37 (d, J=7.9 Hz, 2H), 7.25 (d, J=7.4 Hz, 2H), 7.13 (d, J=7.5 Hz, 1H), 7.09 (d, J=6.8 Hz, 2H), 6.98 (t, J=7.9 Hz, 1H), 6.72 (d, J=7.5 Hz, 1H), 6.66 (d, J=8.1 Hz, 1H), 5.14 (s, 2H), 3.87 (s, 3H), 3.79-3.63 (m, 6H), 2.82 (t, J=6.9 Hz, 2H), 2.35 (s, 2H), 2.20-2.04 (m, 5H), 1.87-1.66 (m, 5H).

Workup

  1. customAfter this time, the reaction mixture was quenched with 1 N NaOH
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by preparative HPLC (PHENOMENEX® Axia Luna column
  7. custom10 min gradient

Sources & evidence

ORD record
ord-09e0ef49eaa44f388f279b425694bdd9
Source dataset
uspto-grants-2015_06
Patent number
US09062028B2

Reaction notes

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