Triethylamine → Ethyl 2-(2-chloro-4-(3-(3-(tetrahydrofuran-3-yloxy)phenyl)ureido)phenyl)acetate

HRID 1023861Notes

Reaction equation

HRID 1023861 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[C:4]([Cl:14])[CH:3]=1.C(N(CC)CC)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.[O:34]1[CH2:38][CH2:37][CH:36]([O:39][C:40]2[CH:41]=[C:42]([CH:44]=[CH:45][CH:46]=2)[NH2:43])[CH2:35]1>ClCCl>[Cl:14][C:4]1[CH:3]=[C:2]([NH:1][C:23]([NH:43][C:42]2[CH:44]=[CH:45][CH:46]=[C:40]([O:39][CH:36]3[CH2:37][CH2:38][O:34][CH2:35]3)[CH:41]=2)=[O:25])[CH:7]=[CH:6][C:5]=1[CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 59419389Ethyl 2-(4-amino-2-chlorophenyl)acetateHCID 635571313-(Tetrahydrofuran-3-yloxy)aniline

Product 1

HCID 67206006Ethyl 2-(2-chloro-4-(3-(3-(tetrahydrofuran-3-yloxy)phenyl)ureido)phenyl)acetateYield 47.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of ethyl 2-(4-amino-2-chlorophenyl)acetate (240 mg, 1.12 mmol) in dry dichloromethane (4 mL), was added triethylamine (3.13 mL, 22.47 mmol) followed by triphosgene (333 mg, 1.12 mmol) solution in dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 1 h. To this mixture was then added 3-(tetrahydrofuran-3-yloxy)aniline (403 mg, 2.25 mmol) in dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 4 h and concentrated. The residue was dissolved in ethyl acetate and washed with water (2×20 mL), brine (10 mL), dried and concentrated. The crude product was purified by flash column chromatography to afford the desired product as a clear oil (221 mg, 0.528 mmol, 47%). 1H NMR: 1.30 (t, 3H, J=7.2 Hz), 2.05-2.15 (m, 2H), 3.68 (s, 2H), 3.81-3.97 (m, 4H), 4.21 (q, 2H, J=7.2 Hz), 4.82 (d, 1H, J=1.6 Hz), 6.49 (dd, 1H, J=8 Hz, 1.6 Hz), 6.71 (d, 1H, J=7.6 Hz), 7.02-7.11 (m, 4H), 7.18 (s, 1H), 7.53 (s, 1H), 7.59 (s, 1H).

Workup

  1. stirringThe reaction mixture was stirred at room temperature for 4 h
  2. concentrationconcentrated
  3. dissolutionThe residue was dissolved in ethyl acetate
  4. washwashed with water (2×20 mL), brine (10 mL)
  5. customdried
  6. concentrationconcentrated
  7. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-e0e3c810dfec45588051f6b01ba973c4
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

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