Diisopropylethylamine → cis(+/-)Tert-butyl-3-azido-4-{[(3,4-dichloro-5-methyl-1h-pyrrol-2-yl)carbonyl]amino}piperidine-1-carboxylate

HRID 1948385Notes

Reaction equation

HRID 1948385 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11]([NH2:14])[CH:10]([N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].CCN(C(C)C)C(C)C.[Cl:27][C:28]1[C:32]([Cl:33])=[C:31]([CH3:34])[NH:30][C:29]=1[C:35](Cl)=[O:36]>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][C@H:11]([NH:14][C:35]([C:29]2[NH:30][C:31]([CH3:34])=[C:32]([Cl:33])[C:28]=2[Cl:27])=[O:36])[C@H:10]([N:15]=[N+:16]=[N-:17])[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 72275737Tert-butyl-4-amino-3-azidopiperidine-1-carboxylate2×HCID 860383943,4-Dichloro-5-methyl-1H-pyrrole-2-carbonyl chloride

Product 1

HCID 131730339cis(+/-)Tert-butyl-3-azido-4-{[(3,4-dichloro-5-methyl-1h-pyrrol-2-yl)carbonyl]amino}piperidine-1-carboxylateYield 69%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Crude tert-butyl-4-amino-3-azidopiperidine-1-carboxylate (Intermediate 270, 3.3 mmol) was dissolved in anhydrous CH2Cl2 (10 ml) and DIEA (1.27 g; 1.6 ml; 9.9 mmol; 3 eq.). The solution was cooled to 0 C and 3,4-dichloro-5-methyl-1H-pyrrole-2-carbonyl chloride (736 mg; 3.5 mmol; 1.05 eq.) was added. The reaction was complete within 30 minutes. Dilute with CH2Cl2 and wash with H2O (×2), brine and dried over Na2SO4. Filter and concentrate. Purify by flash column chromatography (0-60% EtOAc/hexanes). Isolation gave 967 mg in 69% yield over the two-step sequence. LC/MS (ES−)[(M−H)+]: 415, 417 for C16H22Cl2N6O3.

Workup

  1. additionwas added
  2. washwash with H2O (×2), brine
  3. dry with materialdried over Na2SO4
  4. filtrationFilter
  5. concentrationconcentrate
  6. customPurify by flash column chromatography (0-60% EtOAc/hexanes)
  7. customIsolation gave 967 mg in 69% yield over the two-step sequence

Sources & evidence

ORD record
ord-d6caecf170184a9ea001b9e2b0a7715e
Source dataset
uspto-grants-2013_03
Patent number
US08399489B2

Reaction notes

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