Ethyl Acetate → Methyl N-(ethoxycarbonyl)-O-(3'-{[(propylamino)carbonyl]amino}-1,1'-biphenyl-3-yl)-L-serinate

HRID 1265222Notes

Reaction equation

HRID 1265222 reaction equation
Cl.[CH2:2]([NH:5][C:6]([NH:8][C:9]1[CH:10]=[C:11]([C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([O:21][CH2:22][C@@H:23]([C:25]([O:27][CH3:28])=[O:26])[NH2:24])[CH:16]=2)[CH:12]=[CH:13][CH:14]=1)=[O:7])[CH2:3][CH3:4].C(N(CC)C(C)C)(C)C.[NH4+].[Cl-].[C:40]([O:43][CH2:44][CH3:45])(=[O:42])C>C1COCC1>[CH2:44]([O:43][C:40]([NH:24][C@H:23]([C:25]([O:27][CH3:28])=[O:26])[CH2:22][O:21][C:17]1[CH:16]=[C:15]([C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([NH:8][C:6]([NH:5][CH2:2][CH2:3][CH3:4])=[O:7])[CH:10]=2)[CH:20]=[CH:19][CH:18]=1)=[O:42])[CH3:45]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 25517Ammonium ChlorideHCID 81531DiisopropylethylamineHCID 69940921Methyl O-(3'-{[(propylamino)carbonyl]amino}-1,1'-biphenyl-3-yl)-L-serinate Hydrochloride

Product 1

HCID 59050114Methyl N-(ethoxycarbonyl)-O-(3'-{[(propylamino)carbonyl]amino}-1,1'-biphenyl-3-yl)-L-serinate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

The compound of Example 6 (256.0 mg, 0.63 mmol, 1 equiv) was suspended in THF (3 mL) and cooled to 0° C. Ethyl chloroformiate (88.5 mg, 0.82 mmol, 1.3 equiv) was added dropwise followed by N,N diisopropylethylamine (234.3 mg, 1.88 mmol, 3 equiv). The reaction mixture was allowed to warm to room temperature and stirred for one hour. It was worked up by addition of sat. aqueous NH4Cl soln. and ethyl acetate. The phases were separated and the organic layer was dried over NaSO4. After filtration and evaporation of the solvents the crude product was purified by chromatography (SiO2 CH/EtOAc 90:10). Yield 210.0 mg, 75.4% of a white solid. 1H NMR (CDCl3, 300 MHz) δ 7.50 (s, 1H); 7.39-7.25 (m, 3H); 7.21 (d, 1H), 7.12 (d, 1H); 7.05 (s, 1H); 6.90 (brs, 1H); 6.81 (d, 1H); 5.80 (d, 1H); 5.10 (m, 1H); 4.75-4.65 (m, 1H); 4.42 (dd, 1H); 4.25 (dd, 1H); 4.20-4.10 (m, 2H); 3.79 (s, 3H); 3.20 (dd, 2H); 1.52 (sext, 2H); 1.22 (t, 3H); 0.95 (t, 3H). MS (DCI/NH3) 461 (M+NH4), 444 (M+H).

Workup

  1. additionEthyl chloroformiate (88.5 mg, 0.82 mmol, 1.3 equiv) was added dropwise
  2. temperatureto warm to room temperature
  3. customThe phases were separated
  4. dry with materialthe organic layer was dried over NaSO4
  5. filtrationAfter filtration and evaporation of the solvents the crude product
  6. customwas purified by chromatography (SiO2 CH/EtOAc 90:10)

Sources & evidence

ORD record
ord-facb01c9fad74206b3c2418509bb6ea4
Source dataset
uspto-grants-2003_04
Patent number
US06545029B2

Reaction notes

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