Triethylamine → HCID 15952164, compound

HRID 1642241Notes

Reaction equation

HRID 1642241 reaction equation
[Cl:1][C:2]1[CH:17]=[C:16]([Cl:18])[CH:15]=[CH:14][C:3]=1[O:4][C:5]1[CH:13]=[CH:12][CH:11]=[CH:10][C:6]=1[C:7]([OH:9])=O.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][CH:48]([NH2:51])[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:40])[CH3:39]>C(Cl)Cl.CN(C)C1C=CN=CC=1>[C:38]([O:42][C:43]([N:45]1[CH2:50][CH2:49][CH:48]([NH:51][C:7](=[O:9])[C:6]2[CH:10]=[CH:11][CH:12]=[CH:13][C:5]=2[O:4][C:3]2[CH:14]=[CH:15][C:16]([Cl:18])=[CH:17][C:2]=2[Cl:1])[CH2:47][CH2:46]1)=[O:44])([CH3:41])([CH3:39])[CH3:40]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 12682914-Amino-1-Boc-piperidineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 120257772-(2,4-dichlorophenoxy)benzoic acid

Product 1

HCID 15952164HCID 15952164, compoundYield 40%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent3×

Procedure

A solution of 2-(2,4-dichlorophenoxy)benzoic acid (AMR01067, 1.24 g, 4.39 mmol) in dry DCM (20 mL) was stirred under nitrogen, and 4-dimethylaminopyridine (DMPA, 40 mg, 0.327 mmol), (1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC, 2.5, 13.18 mmol) and triethylamine (0.6 mL) were added. The resulting mixture was stirred for 30 min under nitrogen and 4-aminopiperidine-1-carboxylic acid tert-butyl ester (AMR01068, 0.88 g, 4.39 mmol) in dry DCM (410 mL) was added. After stirring at room temperature for 48 h, the mixture was diluted with DCM, washed with HCl (1M, 3×25 mL), water, saturated NaHCO3 (2×25 mL) and brine. The organic layer was dried (MgSO4), filtered and evaporated. Flash chromatography on silica gel of the crude product using DCM/MeOH 99:1 as eluenty gave 4-[2-(2,4-dichlorophenoxy)benzoylamino]piperidine-1-carboxylic acid tert-butyl ester (953 mg, 40%) as white solid. Rf: 0.64 (DCM/MeOH 9:1) 1H NMR (270 MHz, CDCl3) δ 1.48 (9H, s, 3CH3), 1.92 (2H, m, CH2), 2.92 (2H, br t, CH2), 3.95 (2H, br d, CH2), 4.11 (1H, m, CH), 6.78 (1H, dd, J=8.2, 1.0 Hz, ArH), 6.87 (1H, d, J=8.9 Hz, ArH), 7.21 (1H, dd, J=8.6, 2.5 Hz, ArH), 7.25 (1H, m, ArH), 7.35 (1H, br s, NH), 7.40 (1H, m, ArH), 7.50 (1H, d, J=2.5 Hz, ArH) and 8.17 (1H, dd, J=7.9, 2.0 Hz, ArH). LC/MS (APCI) tr=5.36 min, m/z 467.36 (18), 465.41 (M++H, 30), 411.33 (67), 409.38 (M+-C4H8, 100). HPLC tr=2.93 min (97.22%)

Workup

  1. stirringAfter stirring at room temperature for 48 h
  2. washwashed with HCl (1M, 3×25 mL), water, saturated NaHCO3 (2×25 mL) and brine
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. customevaporated

Sources & evidence

ORD record
ord-4fbcf56c5e4f4e6492bf1073715f28db
Source dataset
uspto-grants-2012_02
Patent number
US08119627B2

Reaction notes

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