Dichloroisoproterenol → (4-{3-[2-(3,4-Dichloro-phenyl)-2-hydroxy-ethyl]-3-isopropyl-ureido}-benzyl)-carbamic acid tert-butyl ester

HRID 1057977Notes

Reaction equation

HRID 1057977 reaction equation
ClC(Cl)([O:4][C:5](=O)[O:6]C(Cl)(Cl)Cl)Cl.[NH2:13][C:14]1[CH:21]=[CH:20][C:17]([CH2:18][NH2:19])=[CH:16][CH:15]=1.[C:22]([NH:26][C:27](=[O:29])[O-])([CH3:25])([CH3:24])C.C(N([CH:36]([CH3:38])[CH3:37])CC)(C)C.C(N[CH2:43][CH:44]([C:46]1[CH:51]=[CH:50][C:49]([Cl:52])=[C:48]([Cl:53])[CH:47]=1)[OH:45])(C)C.[CH2:54](Cl)Cl>CCOC(C)=O>[C:36]([O:6][C:5](=[O:4])[NH:19][CH2:18][C:17]1[CH:20]=[CH:21][C:14]([NH:13][C:27]([N:26]([CH2:43][CH:44]([C:46]2[CH:51]=[CH:50][C:49]([Cl:52])=[C:48]([Cl:53])[CH:47]=2)[OH:45])[CH:22]([CH3:24])[CH3:25])=[O:29])=[CH:15][CH:16]=1)([CH3:38])([CH3:54])[CH3:37]

Participants

8

Reactant 6

HCID 5806DichloroisoproterenolHCID 6344Dichloromethane3×HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 4278144-AminobenzylamineHCID 21252905Tert-butylcarbamate

Product 1

HCID 23560247(4-{3-[2-(3,4-Dichloro-phenyl)-2-hydroxy-ethyl]-3-isopropyl-ureido}-benzyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 0.89 g (3 mmol) triphosgene in 10 ml CH2Cl2 was added a solution of 2.0 g (8 mmol) 4-aminobenzylamine, tertbutylcarbamate and 1.69 ml (9.7 mmol) diisopropylethylamine in 25 ml CH2Cl2 dropwise over 1 hour. After the addition was complete, a solution of 1.79 g (8 mmol) 2-isopropylamino-1-(3,4-dichlorophenyl)-ethanol and 1.69 ml (9.7 mmol) diisopropylethylamine in 25 ml CH2Cl2 was added over 5 min. The reaction mixture was stirred for 10 min. diluted with 200 ml EtOAc, washed with 200 ml each of saturated aqueous NaHCO3, water, and brine, then dried over Na2SO4 , filtered and concentrated. Purification by flash chromatography (50% EtOAc/hexanes) provided 4 g (4-{3-[2-(3,4-Dichloro-phenyl)-2-hydroxy-ethyl]-3-isopropyl-ureido}-benzyl)-carbamic acid tert-butyl ester. 1H NMR (300 mHz, CDCl3) 8.85 (br s, 1H); 7.45 (m, 2H); 7.3-7.0 (m, 5H); 5.82 (s, 1H); 5.12 (br s, 1H); 4.7 (d, 1H, J=8 Hz); 4.4-4.15 (m, 3H); 3.42 (dd, 1H, J=16 and 8 Hz); 3.1 (d, 1H, J=16 Hz); 1.4 (s, 9H); 1.9 (d, 3H, J=7 Hz); 1.07 (d, 3H, J=7 Hz).

Workup

  1. additionAfter the addition
  2. washwashed with 200 ml each of saturated aqueous NaHCO3, water, and brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customPurification by flash chromatography (50% EtOAc/hexanes)

Sources & evidence

ORD record
ord-e1d3fd509dbc4835ae3bc74edbf4c248
Source dataset
uspto-grants-2003_02
Patent number
US06515023B2

Reaction notes

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