Triethylamine → HCID 69141286, compound

HRID 914765Notes

Reaction equation

HRID 914765 reaction equation
[NH:1]([C:9]([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10])[C@@H:2]([C:6]([OH:8])=O)[CH:3]([CH3:5])[CH3:4].Br.Br.[CH3:18][N:19]1[CH2:24][CH2:23][CH:22]([CH:25]2[CH2:30][CH2:29][NH:28][CH2:27][CH2:26]2)[CH2:21][CH2:20]1.C(N(CC)CC)C.C1C=CC2N(O)N=NC=2C=1.C1CCC(N=C=NC2CCCCC2)CC1.[Li+].[Cl-]>CN(C=O)C>[C:9]([NH:1][C@@H:2]([C:6]([N:28]1[CH2:29][CH2:30][CH:25]([CH:22]2[CH2:21][CH2:20][N:19]([CH3:18])[CH2:24][CH2:23]2)[CH2:26][CH2:27]1)=[O:8])[CH:3]([CH3:4])[CH3:5])([O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[O:10]

Participants

8

Reactant 6

HCID 8471TriethylamineHCID 10868DicyclohexylcarbodiimideHCID 757711-HydroxybenzotriazoleHCID 433294Lithium ChlorideHCID 637605(2R)-2-(((tert-butoxy)carbonyl)amino)-3-methylbutanoic acidHCID 21935434HCID 21935434, compound2×

Product 1

HCID 69141286HCID 69141286, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of Boc-D-Val-OH (33.0 g, 152 mmol) in anhydrous DMF (1.5 L) is added 4-(1-methylpiperidin-4-yl)-piperidine dihydrobromide (52.2 g, 152 mmol) [4-(1-methyl-piperidin-4-yl)piperidine dihydrobromide is also named 1-methyl-4,4′-bispiperidine dihydrobromide; and its preparation is described in WO 00/76971 at pages 163-164.] followed by triethylamine (63.5 mL, 456 mmol), HOBt (20.5 g, 152 mmol) and DCC (31.3 g, 152 mmol) at room temperature. The reaction is allowed to stir at room temperature overnight. The mixture is then poured into aqueous LiCl (1.5 L) and extracted with CH2Cl2 (3×2 L). The organic layers are combined, dried over Na2SO4, filtered and concentrated in vacuo. The residue is dissolved in CHCl3 (1 L), filtered and concentrated in vacuo. The crude material is purified using chromatography over silica gel, eluting with 4% (2 M NH3 in MeOH)/CHCl3 to give 43.3 g (75%) of the title compound as a tan foam.

Workup

  1. customand its preparation
  2. extractionextracted with CH2Cl2 (3×2 L)
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue is dissolved in CHCl3 (1 L)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customThe crude material is purified
  10. washeluting with 4% (2 M NH3 in MeOH)/CHCl3

Sources & evidence

ORD record
ord-aa32508e26a24fc09a9230d073c232af
Source dataset
uspto-grants-2007_09
Patent number
US07265121B2

Reaction notes

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