1,2-Dichloroethane → Tert-butyl 4-(cyclopropylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-ylcarbamate

HRID 1474144Notes

Reaction equation

HRID 1474144 reaction equation
C(Cl)CCl.C1C=C[C:8]2N(O)N=[N:11][C:9]=2[CH:10]=1.CCN(CC)CC.[C:22]([O:26][C:27]([NH:29][CH:30]([CH2:36][C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)[CH:31]([OH:35])[C:32]([OH:34])=O)=[O:28])([CH3:25])([CH3:24])[CH3:23].C1(N)CC1>C(Cl)Cl>[CH:9]1([NH:11][C:32](=[O:34])[CH:31]([OH:35])[CH:30]([NH:29][C:27](=[O:28])[O:26][C:22]([CH3:23])([CH3:24])[CH3:25])[CH2:36][C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[CH2:10][CH2:8]1

Participants

7

Reactant 5

HCID 111,2-Dichloroethane2×HCID 8471Triethylamine2×HCID 69828Cyclopropylamine2×HCID 757711-Hydroxybenzotriazole2×HCID 34203793-tert-Butoxycarbonylamino-2-hydroxy-4-phenylbutyric acid

Product 1

HCID 66645006Tert-butyl 4-(cyclopropylamino)-3-hydroxy-4-oxo-1-phenylbutan-2-ylcarbamateYield 85%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

EDC (8.3 g, 43.3 mmol), HOBT (6.6 g, 43.1 mmol) and Et3N (7 ml, 50.2 mmol) were added to a mixture of 3-(tert-butoxycarbonylamino)-2-hydroxy-4-phenylbutanoic acid (10.6 g, 35.9 mmol) and cyclopropylamine (3.3 ml, 47.6 mmol) in DCM (300 mL) at 5° C. The reaction mixture was allowed to warm to room temperature and stirred overnight. After cooling to 5° C. more cyclopropylamine (2 ml, 28.5 mmol), EDC (5 g, 26.1 mmol), HOBT (4 g, 26.1 mmol) and Et3N (3.5 ml, 25.1 mmol) were added, the mixture was allowed to warm to room temperature and the stirring was continued overnight. DCM (300 mL) was added, followed by washing with 0.5 M aqueous HCl solution, brine and drying with MgSO4. The crude product was recrystallized from methyl-tert-butylether, the crystals obtained were washed with n-pentane and dried providing the title compound (10.2 g, 85%).

Workup

  1. additionwere added
  2. temperatureto warm to room temperature
  3. waitthe stirring was continued overnight
  4. washby washing with 0.5 M aqueous HCl solution, brine
  5. dry with materialdrying with MgSO4
  6. customThe crude product was recrystallized from methyl-tert-butylether
  7. customthe crystals obtained
  8. washwere washed with n-pentane
  9. customdried

Sources & evidence

ORD record
ord-585f2016e8064d7e8fff54ebff2f60a5
Source dataset
uspto-grants-2015_04
Patent number
US09018206B2

Reaction notes

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