Triethylamine → Ethyl 2-(4-(3-(2-(tert-butoxycarbonylamino)cyclohexyl)ureido)-2-chlorophenyl)acetate

HRID 1023859Notes

Reaction equation

HRID 1023859 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.[NH2:34][CH:35]1[CH2:40][CH2:39][CH2:38][CH2:37][CH:36]1[NH:41][C:42](=[O:48])[O:43][C:44]([CH3:47])([CH3:46])[CH3:45]>ClCCl>[C:44]([O:43][C:42]([NH:41][CH:36]1[CH2:37][CH2:38][CH2:39][CH2:40][CH:35]1[NH:34][C:23](=[O:25])[NH: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)=[O:48])([CH3:45])([CH3:47])[CH3:46]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 94429TriphosgeneHCID 3268011tert-Butyl (2-aminocyclohexyl)carbamateHCID 59419389Ethyl 2-(4-amino-2-chlorophenyl)acetate

Product 1

HCID 67204990Ethyl 2-(4-(3-(2-(tert-butoxycarbonylamino)cyclohexyl)ureido)-2-chlorophenyl)acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of ethyl 2-(4-amino-2-chlorophenyl)acetate (178 mg, 0.833 mmol) in dry dichloromethane (5 mL), was added triethylamine (2.32 mL, 16.66 mmol) followed by triphosgene (247 mg, 0.833 mmol) solution in dichloromethane (1 mL). The reaction mixture was stirred at room temperature for 1 h. To this mixture was then added tert-butyl 2-aminocyclohexylcarbamate (357 mg, 1.67 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 mixture of cis and trans diastereomers (220 mg, 0.485 mmol, 58%). 1H NMR: 1.23-1.28 (m, 6H), 1.38 (s, 9H), 1.70-1.73 (m, 2H), 2.01-2.08 (m, 2H), 3.29-3.32 (m, 1H), 3.53-3.58 (m, 1H), 3.68 (s, 2H), 4.11-4.19 (m, 2H), 5.01 (d, 1H, J=8.8 Hz), 5.57 (d, 1H, J=8 Hz), 7.13 (d, 1H, J=8.4 Hz), 7.20 (d, 1H, J=6.8 Hz), 7.41 (s, 1H), 7.46 (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-45423655ff5b4e95a0d7ba40524bab19
Source dataset
uspto-grants-2014_05
Patent number
US08722720B2

Reaction notes

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