4-Methylmorpholine → Boc-Ala-Ala-NH-(CH2)4-OH

HRID 1044646

Reaction equation

HRID 1044646 reaction equation
[C:1]([NH:8][C@H:9]([C:11]([NH:13][C@H:14]([C:16]([OH:18])=O)[CH3:15])=[O:12])[CH3:10])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.ClC(OCC)=O.[NH2:32][CH2:33][CH2:34][CH2:35][CH2:36][OH:37]>C1COCC1>[NH:8]([C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])[C@H:9]([C:11]([NH:13][C@H:14]([C:16]([NH:32][CH2:33][CH2:34][CH2:35][CH2:36][OH:37])=[O:18])[CH3:15])=[O:12])[CH3:10]

Participants

6

Reactant 4

HCID 79724-Methylmorpholine2×HCID 10928Ethyl chloroformateHCID 258684-Amino-1-butanolHCID 6992569N-((1,1-Dimethylethoxy)carbonyl)-L-alanyl-L-alanine

Product 1

HCID 59537080Boc-Ala-Ala-NH-(CH2)4-OHYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a vigorously stirring solution of Boc-(Ala)2-OH (0.9 gm, 3.46 mmol) and NMM (0.57 mL, 5.2 mmol) in THF (20 mL) cooled to −15° C. was added under N2 atmosphere ethyl chloroformate (ECF) (372 μL, 3.56 mmol) and stirred for 2 min. A solution of H2N(CH2)4OH (462 mg, 5.19 mmol) in THF (5 mL) was added to the mixture followed by NMM (950 μL, 8.65 mmol) and the mixture was warmed to r.t. and stirred until silica gel TLC indicated complete consumption of the starting acid (eluting solvent—MeOH:DCM—1:10, Rf—0.45) (˜8 h). The solvent was evaporated, and the residue was diluted with EtOAc and washed with brine, water, saturated solutions of citric acid and NaHCO3, and the organic layer was dried using NaHSO4, and the solvent was removed under vacuum to yield a residue which was purified using silica gel flash column chromatography—Hexanes:EtOAc—1:3; to give the desired product in 75% yield (858 mg) as a solid—m.p.—102-104° C.

Workup

  1. stirringstirred until silica gel
  2. customconsumption of the starting acid (eluting solvent—MeOH:DCM—1:10, Rf—0.45) (˜8 h)
  3. customThe solvent was evaporated
  4. additionthe residue was diluted with EtOAc
  5. washwashed with brine, water, saturated solutions of citric acid and NaHCO3
  6. customthe organic layer was dried
  7. customthe solvent was removed under vacuum
  8. customto yield a residue which
  9. customwas purified

Sources & evidence

ORD record
ord-bd9d8cd11099458aa2f8c3dce2987f7f
Source dataset
uspto-grants-2013_10
Patent number
US08563686B2

Linked notes

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