Diisopropylethylamine → (S)-1-isopropyl-4-[1-(tert-Butoxycarbonyl)-piperidine-4-carbonyl]-2-methyl piperazine

HRID 734334Notes

Reaction equation

HRID 734334 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([C:14]([OH:16])=O)[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C1C=NC2N(O)N=NC=2C=1.Cl.[CH:28]([N:31]1[CH2:36][CH2:35][NH:34][CH2:33][C@@H:32]1[CH3:37])([CH3:30])[CH3:29].C(N(CC)C(C)C)(C)C>CN(C=O)C.O.C(Cl)CCl>[CH:28]([N:31]1[CH2:36][CH2:35][N:34]([C:14]([CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[CH2:13][CH2:12]2)=[O:16])[CH2:33][C@@H:32]1[CH3:37])([CH3:30])[CH3:29]

Participants

8

Reactant 4

HCID 81531DiisopropylethylamineHCID 181649HOAtHCID 3928711-(tert-Butoxycarbonyl)-4-piperidinecarboxylic acidHCID 68816141(S)-1-isopropyl-2-methyl piperazine hydrochloride

Product 1

HCID 68818623(S)-1-isopropyl-4-[1-(tert-Butoxycarbonyl)-piperidine-4-carbonyl]-2-methyl piperazineYield 96%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

1-(tert-Butoxycarbonyl)-piperidine4-carboxylic acid (3.2 g) in dry DMF (30 ml) was treated first with EDC (5.4 g) and catalytic HOAt followed by (S)-1-isopropyl-2-methyl piperazine hydrochloride (D27)(2 g) and N,N-diisopropylethylamine (5 ml). After the reaction mixture was stirred overnight, water (50 ml) was added and the cloudy precipitate was extracted into EtOAc (2×25 ml), dried (MgSO4) and filtered. The filtrate was absorbed on silica and purified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]. The fractions containing the required product were evaporated to give the title compound (D28) as an oil (3.8 g). LCMS electrospray (+ve) 354 (MH+).

Workup

  1. extractionthe cloudy precipitate was extracted into EtOAc (2×25 ml)
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. customThe filtrate was absorbed on silica
  5. custompurified by column chromatography [silica gel, step gradient 0-10% MeOH (containing 10% 0.88 ammonia solution) in DCM]
  6. additionThe fractions containing the required product
  7. customwere evaporated

Sources & evidence

ORD record
ord-16d4861e2e024ebea859845f34b0f8e8
Source dataset
uspto-grants-2009_09
Patent number
US07592347B2

Reaction notes

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