Potassium Carbonate → tert-Butyl 4-{[({[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}amino)carbonyl]amino}butanoate

HRID 1371389Notes

Reaction equation

HRID 1371389 reaction equation
Cl.[C:2]([O:6][C:7](=[O:12])[CH2:8][CH2:9][CH2:10][NH2:11])([CH3:5])([CH3:4])[CH3:3].[Cl:13][C:14]1[CH:15]=[C:16]([CH:38]=[CH:39][C:40]=1[Cl:41])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][C@@H:20]([CH2:24][NH:25][C:26](=O)[O:27]C2C=CC([N+]([O-])=O)=CC=2)[CH2:19]1.C(N(CC)C(C)C)(C)C.C(=O)([O-])[O-].[K+].[K+]>ClCCl>[Cl:13][C:14]1[CH:15]=[C:16]([CH:38]=[CH:39][C:40]=1[Cl:41])[CH2:17][N:18]1[CH2:23][CH2:22][O:21][C@@H:20]([CH2:24][NH:25][C:26]([NH:11][CH2:10][CH2:9][CH2:8][C:7]([O:6][C:2]([CH3:5])([CH3:3])[CH3:4])=[O:12])=[O:27])[CH2:19]1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 81531DiisopropylethylamineHCID 117750244-Nitrophenyl [(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methylcarbamateHCID 24750478Tert-butyl 4-aminobutanoate hydrochloride

Product 1

HCID 86760343tert-Butyl 4-{[({[(2S)-4-(3,4-dichlorobenzyl)morpholin-2-yl]methyl}amino)carbonyl]amino}butanoateYield 75%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
22 °C

Procedure

4-Aminobutyric acid tert-butyl ester hydrochloride (0.235 g) was added to a stirred solution of Intermediate 13 (0.440 g) and N,N-diisopropylethylamine (0.42 ml) in dry dichloromethane (20 ml) under nitrogen, and the mixture was stirred at 22° C. for 18 h. The mixture was treated with saturated aqueous potassium carbonate (20 ml) and stirred for 5 min. The layers were separated and the organic layer applied to a silica gel cartridge (10 g Varian Bond Elut). Elution with dichloromethane, ether, ethyl acetate, and acetone gave the crude product (0.357 g). Further purification by chromatography on silica gel (10 g Varian Bond Elut cartridge), eluting with dichloromethane (1 column volume), ether (4 column volumes) and ethyl acetate (8 column volumes) gave the title compound as a gum (0.345 g).

Workup

  1. stirringstirred for 5 min
  2. customThe layers were separated
  3. washElution with dichloromethane, ether, ethyl acetate, and acetone
  4. customgave the crude product (0.357 g)
  5. customFurther purification by chromatography on silica gel (10 g Varian Bond Elut cartridge)
  6. washeluting with dichloromethane (1 column volume), ether (4 column volumes) and ethyl acetate (8 column volumes)

Sources & evidence

ORD record
ord-244ca70a9aa544318514685e5b6668d6
Source dataset
uspto-grants-2007_01
Patent number
US07157457B2

Reaction notes

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