4-Methylmorpholine → N1-[1(RS)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]-L-leucinamide

HRID 850876Notes

Reaction equation

HRID 850876 reaction equation
C(OC(CCC(N[C@H](C(N[C@H](C([NH:37][C@H:38]([C:47]([NH:49][C@H:50](C(N[C@H](C(O)=O)CC(C)C)=O)[C:51]([CH3:54])(C)C)=[O:48])[CH2:39][C:40]1[CH:45]=CC=C[C:41]=1C)=O)CCC(=O)OC(C)(C)C)=O)CC(=O)OC(C)(C)C)=O)=O)(C)(C)C.CN1CCOCC1.ClC(OCC(C)C)=O.FC(F)(F)C(O)=O.C(C([B:92]1[O:96][C:95]([CH3:98])([CH3:97])[C:94]([CH3:100])([CH3:99])[O:93]1)N)C>CN(C)C=O.ClCCl>[CH3:99][C:94]1([CH3:100])[C:95]([CH3:98])([CH3:97])[O:96][B:92]([CH:50]([NH:49][C:47](=[O:48])[C@H:38]([CH2:39][CH:40]([CH3:41])[CH3:45])[NH2:37])[CH2:51][CH3:54])[O:93]1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 19364709a-(RS)-ethyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-methylamine trifluoroacetateHCID 22942121N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-alpha-aspartyl]-O-tert-butyl-L-alpha-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine

Product 1

HCID 131721619N1-[1(RS)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]-L-leucinamide

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
-15 °C

Procedure

0.25 g (0.27 mmol) of N-[N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-L-leucine was dissolved in 2 ml of dimethylformamide and 5 ml of dichloromethane. 0.15 ml (1.6 mmol) of N-methylmorpholine was added and the solution was cooled to -15° C. under a nitrogen atmosphere. 50 mg (0.38 mmol) of isobutyl chloroformate were added and the solution was stirred for 10 minutes at -15° C. 0.1 g (0.33 mmol) of α-(RS)-ethyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane-2-methylamine trifluoroacetate was added and the mixture was stirred at room temperature for 18 hours. After evaporation the residue was partitioned between ethyl acetate and 2M hydrochloric acid. The organic layer was washed with 2M hydrochloric acid, water and saturated sodium chloride solution and then dried over anhydrous sodium sulphate. After evaporation there was obtained 0.26 g of N2-N-[N-[N-[N-[3-(tert-butoxycarbonyl)propionyl]-O-tert-butyl-L-α-aspartyl]-O-tert-butyl-L-α-glutamyl]-2-methyl-L-phenylalanyl]-3-methyl-L-valyl]-N1-[1(RS)-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propyl]-L-leucinamide in the form of a solid; MS: m/e 1085 [M+H].

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hours
  2. customAfter evaporation the residue
  3. customwas partitioned between ethyl acetate and 2M hydrochloric acid
  4. washThe organic layer was washed with 2M hydrochloric acid, water and saturated sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulphate
  6. customAfter evaporation

Sources & evidence

ORD record
ord-563a59da049a40c6b865aa452206cf2d
Source dataset
uspto-grants-2000_01
Patent number
US06018020

Reaction notes

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