1,2-Dichloroethane → tert-butyl (2S)-2-({[5-chloro-2-(1H-tetraazol-1-yl)benzyl]amino}carbonyl)piperidine-1-carboxylate

HRID 857799Notes

Reaction equation

HRID 857799 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([N:26]2[CH:30]=[N:29][N:28]=[N:27]2)=[C:22]([CH2:24][NH2:25])[CH:23]=1.C(Cl)CCl.C1C=NC2N(O)N=NC=2C=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.O>[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([N:26]2[CH:30]=[N:29][N:28]=[N:27]2)=[C:22]([CH:23]=1)[CH2:24][NH:25][C:14]([C@@H:9]1[CH2:10][CH2:11][CH2:12][CH2:13][N:8]1[C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])=[O:16]

Participants

8

Reactant 5

HCID 111,2-DichloroethaneHCID 11430Potassium CarbonateHCID 181649HOAtHCID 688617(2S)-1-((tert-butoxy)carbonyl)piperidine-2-carboxylic acidHCID 113217565-Chloro-2-(1H-tetrazol-1-yl)benzenemethanamine

Product 1

HCID 86591818tert-butyl (2S)-2-({[5-chloro-2-(1H-tetraazol-1-yl)benzyl]amino}carbonyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

A mixture of (2S)-1-(tert-butoxycarbonyl)piperidine-2-carboxylic acid (299 mg, 1.30 mmol), 1-[5-chloro-2-(1H-tetraazol-1-yl)phenyl]methanamine (293 mg, 1.40 mmol), EDC (376 mg, 1.96 mmol) and HOAt (89 mg, 0.65 mmol) in DMF (7 mL) was stirred at room temperature for 16 h. Water and saturated aqueous K2CO3 were added and the mixture was extracted with EtOAc. The organic layer was washed with brine and the combined aqueous layers were extracted once with CH2Cl2. The combined organic extracts were dried (Na2SO4) and concentrated to a yellow oil. Silica gel chromatography (65% EtOAc-hexanes) afforded the title compound as a light yellow foam. 1H NMR (400 MHz, CDCl3): δ 8.99 (s, 1 H), 7.60 (d, J=1.8 Hz, 1 H), 7.46 (dd, J=1.8, 8.4 Hz, 1 H), 7.29–7.26 (m, 1 H), 6.84 (br m, 1 H), 4.74 (br m, 1 H), 4.29–4.16 (m, 2 H), 4.04 (br m, 1 H), 2.76–2.70 (m, 1 H), 2.24–2.04 (m, 1 H), 1.64–1.32 (br m, 5 H), 1.48 (s, 9 H).

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. extractionthe combined aqueous layers were extracted once with CH2Cl2
  4. dry with materialThe combined organic extracts were dried (Na2SO4)
  5. concentrationconcentrated to a yellow oil

Sources & evidence

ORD record
ord-d7c97b40ff2e443d90f12d558d57533d
Source dataset
uspto-grants-2006_12
Patent number
US07144899B2

Reaction notes

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