Triethylamine → HCID 131729733, compound

HRID 1926707Notes

Reaction equation

HRID 1926707 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([CH:22]=[CH:23][CH:24]=1)[O:6][C:7]1[CH:8]=[C:9]([C:16]([N+:19]([O-])=[O:20])=[CH:17][CH:18]=1)[CH2:10][C@@H:11]([C:13](O)=[O:14])[NH2:12])#[N:2].O.O.[Sn](Cl)[Cl:28].C(N(CC)CC)C.O(C(OC(C)(C)C)=O)C(OC(C)(C)C)=O>C1COCC1.CO>[ClH:28].[NH2:12][C@H:11]1[CH2:10][C:9]2[C:16](=[CH:17][CH:18]=[C:7]([O:6][C:5]3[CH:4]=[C:3]([CH:24]=[CH:23][CH:22]=3)[C:1]#[N:2])[CH:8]=2)[N:19]([OH:20])[C:13]1=[O:14]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 61436Stannous chloride dihydrateHCID 90495Di-tert-butyl dicarbonateHCID 68781090HCID 68781090, compound

Product 1

HCID 131729733HCID 131729733, compoundYield 92.1%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

tert-Butyl [(3S)-1-[(tert-butoxycarbonyl)oxy]-6-(3-cyanophenoxy)-2-oxo-1,2,3,4-tetrahydroquinolin-3-yl]carbonate (88) Sodium acetate trihydrate (4.9 g, 36.3 mmol) was added to a 0° C. solution of 3-(3-cyanophenoxy)-6-nitro-L-phenylalanine (87) (1.3 g, 3.6 mmol) in THF (50 mL) and MeOH (50 mL). The mixture was stirred until all of the salts dissolved, and tin(II) chloride dihydrate (4.2 g, 18.1 mmol) was added. The reaction suspension was stirred at 0° C. for 6 h. Triethylamine (5.1 mL, 36.3 mmol) and BOC2O (1.9 g, 8.7 mmol) were added and the mixture was allowed to stir for 18 h at RT. The reaction mixture was concentrated in vacuo, and the resulting residue was slurried in EtOAc. Insoluble solids were filtered off and washed with EtOAc, and the combined EtOAc fractions were washed with water and concentrated in vacuo. The resulting residue was purified by silica gel chromatography (Gradient: 0% to 50% EtOAc in heptane) to afford the title compound as a white solid (1.1 g, 61%). LCMS m/z 496.2 (M+1). 1H NMR (400 MHz, CDCl3) δ 1.47 (s, 9H), 1.58 (br s, 9H), 2.98 (br dd, J=14, 14 Hz, 1H), 3.41 (v br d, J=14 Hz, 1H), 4.51-4.60 (m, 1H), 5.59 (br s, 1H), 6.91 (br s, 1H), 6.97 (br dd, J=8.5, 2.6 Hz, 1H), 7.0-7.2 (v br s, 1H), 7.19-7.25 (m, 2H), 7.38-7.47 (m, 2H).

Workup

  1. dissolutiondissolved
  2. stirringThe reaction suspension was stirred at 0° C. for 6 h
  3. stirringto stir for 18 h at RT
  4. concentrationThe reaction mixture was concentrated in vacuo
  5. filtrationInsoluble solids were filtered off
  6. washwashed with EtOAc
  7. washthe combined EtOAc fractions were washed with water
  8. concentrationconcentrated in vacuo
  9. customThe resulting residue was purified by silica gel chromatography (Gradient: 0% to 50% EtOAc in heptane)

Sources & evidence

ORD record
ord-745410ce349746b3bc3ea983e3f94dbb
Source dataset
uspto-grants-2012_05
Patent number
US08183238B2

Reaction notes

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