Diisopropylethylamine → tert-Butyl {(2S)-4-[1-(3,4-dichlorophenyl)ethyl]morpholin-2-yl}methylcarbamate

HRID 1371394Notes

Reaction equation

HRID 1371394 reaction equation
[NH:1]1[CH2:6][CH2:5][O:4][C@@H:3]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[CH2:2]1.C(N(CC)C(C)C)(C)C.Br[CH:26]([C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([Cl:35])[CH:29]=1)[CH3:27].C(=O)([O-])O.[Na+]>CN(C)C=O.ClCCl>[Cl:35][C:30]1[CH:29]=[C:28]([CH:26]([N:1]2[CH2:6][CH2:5][O:4][C@@H:3]([CH2:7][NH:8][C:9](=[O:15])[O:10][C:11]([CH3:12])([CH3:14])[CH3:13])[CH2:2]2)[CH3:27])[CH:33]=[CH:32][C:31]=1[Cl:34]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 516892Sodium BicarbonateHCID 42556135(R)-2-N-Boc-aminomethylmorpholineHCID 431414504-(1-Bromoethyl)-1,2-dichlorobenzene2×

Product 1

HCID 86760345tert-Butyl {(2S)-4-[1-(3,4-dichlorophenyl)ethyl]morpholin-2-yl}methylcarbamateYield 89.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

tert-Butyl (2R)-morpholin-2-ylmethylcarbamate (2.00 g) in N,N-dimethylformamide (16 ml) was treated with N,N-diisopropylethylamine (1.6 ml) followed by 4-(1-bromoethyl)-1,2-dichlorobenzene (2.58 g). After stirring for five days at room temperature, further portions of 4-(1-bromoethyl)-1,2-dichlorobenzene (2.58 g) and N,N-diisopropylethylamine (1.6 ml) were added and stirring continued for 24 h at room temperature. The solution was treated with dichloromethane (70 ml) and saturated aqueous sodium hydrogen carbonate (30 ml) and the mixture shaken vigorously. The organic phase was separated and applied equally onto sulphonic acid ion exchange cartridges (5×10 g Isolute SCX, pre-treated with methanol). The cartridges were each eluted with methanol (one column volume) followed by 10% 0.880 ammonia in methanol (one column volume); evaporation in vacuo of the combined basic fractions gave the title compound as a clear colourless gum (3.22 g)

Workup

  1. stirringstirring
  2. waitcontinued for 24 h at room temperature
  3. stirringthe mixture shaken vigorously
  4. customThe organic phase was separated
  5. additionapplied equally onto sulphonic acid ion exchange cartridges (5×10 g Isolute SCX, pre-treated with methanol)
  6. washeach eluted with methanol (one column volume)
  7. customevaporation in vacuo of the combined basic fractions

Sources & evidence

ORD record
ord-b612c8159f0845df961c389628989303
Source dataset
uspto-grants-2007_01
Patent number
US07157457B2

Reaction notes

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