Trifluoroacetic acid → Boc-Ala-Ala-Ala-NH-(CH2)3-Br

HRID 76318Notes

Reaction equation

HRID 76318 reaction equation
[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([OH:6])=O)[CH3:3].CN1CCOCC1.C(O)(C(F)(F)F)=O.[NH2:28][C@H:29]([C:31]([NH:33][C@H:34]([C:36]([NH:38][CH2:39][CH2:40][CH2:41][Br:42])=[O:37])[CH3:35])=[O:32])[CH3:30]>C1COCC1.CCOC(C)=O.CN(C=O)C>[NH:1]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[C@H:2]([C:4]([NH:28][C@H:29]([C:31]([NH:33][C@H:34]([C:36]([NH:38][CH2:39][CH2:40][CH2:41][Br:42])=[O:37])[CH3:35])=[O:32])[CH3:30])=[O:6])[CH3:3]

Participants

8

Reactant 4

HCID 6422Trifluoroacetic acidHCID 79724-Methylmorpholine2×HCID 85082Tert-butoxycarbonylalanineHCID 59479639HCID 59479639, compound

Product 1

HCID 59479644Boc-Ala-Ala-Ala-NH-(CH2)3-Br

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a cold (−15° C.) solution of Boc-Ala-OH (118 mg, 0.63 mmol) and NMM (103 μl, 1.03 mmol) in THF (8 mL) was added ECF (61 μl, 0.64 mmol) and stirred vigorously. After 2 min. a solution of the TFA salt of Ala-Ala-NH(CH2)3—Br (270 mg, 0.69 mmol) in a mixture of THF:DMF (4 mL: 2 mL) was added to it followed by NMM (170 μL, 1.7 mmol) and stirred for further 30 minutes. The mixture was warmed to r.t. and stirred for 6 h. The solvent was removed under reduced pressure to give a residue which was diluted with EtOAc and washed with saturated citric acid, saturated NaHCO3 and the organic layer was dried over Na2SO4 and concentrated under vacuum to give a residue, which was purified by silica gel flash column chromatography (EtOAc:Hexanes—9:1) to give the desired product as a solid (m.p.—decomposed at 192° C.) in moderate yields (137 mg, 54%). TLC (MeOH:DCM—1:9; Rf—0.44).

Workup

  1. stirringstirred for further 30 minutes
  2. stirringstirred for 6 h
  3. customThe solvent was removed under reduced pressure
  4. customto give a residue which
  5. washwashed with saturated citric acid, saturated NaHCO3
  6. dry with materialthe organic layer was dried over Na2SO4
  7. concentrationconcentrated under vacuum
  8. customto give a residue, which
  9. customwas purified by silica gel flash column chromatography (EtOAc:Hexanes—9:1)

Sources & evidence

ORD record
ord-674606da995f41a3bda2d37ce1fd701c
Source dataset
uspto-grants-2014_09
Patent number
US08835602B2

Reaction notes

Loading…