Triethylamine → 4-(4-(Cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde

HRID 1467541Notes

Reaction equation

HRID 1467541 reaction equation
[CH:1]([C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1)=[O:2].C(N(CC)CC)C.ON1C2C=CC=CC=2N=N1.Cl.C(N=C=NCCCN(C)C)C.Cl.[CH:42]1([C:45]([N:47]2[CH2:52][CH2:51][NH:50][CH2:49][CH2:48]2)=[O:46])[CH2:44][CH2:43]1>ClCCl>[CH:42]1([C:45]([N:47]2[CH2:52][CH2:51][N:50]([C:7]([C:6]3[CH:5]=[CH:4][C:3]([CH:1]=[O:2])=[CH:11][CH:10]=3)=[O:9])[CH2:49][CH2:48]2)=[O:46])[CH2:43][CH2:44]1

Participants

7

Reactant 5

HCID 8471TriethylamineHCID 120884-Formylbenzoic acidHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 208479551-(Cyclopropylcarbonyl)piperazine Hydrochloride

Product 1

HCID 866390294-(4-(Cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehydeYield 80%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred mixture of 4-formylbenzoic acid (900 mg, 6 mmol) in anhydrous dichloromethane (30 mL) was added triethylamine (1.52 mg, 15 mmol), 1-hydroxybenzotriazole (891 mg, 6.6 mmol), followed by 1-ethyl-3-(3-dimethylamino propyl)carbodiimide hydrochloride (1.254 g, 6.6 mmol). After the addition, the mixture was stirred at room temperature for 40 mins. Then the mixture was cooled to 0° C. and cyclopropyl(piperazin-1-yl)methanone hydrochloride (1.259 g, 6.6 mmol) was added in portion-wise. After the addition, the mixture was allowed to stir at room temperature overnight. The mixture was diluted with dichloromethane (50 mL), washed with saturated citric acid (100 mL×2), followed by saturated sodium bicarbonate (100 mL×2), brine (50 mL), dried over anhydrous sodium sulfate, and concentrated to give 4-(4-(cyclopropanecarbonyl)piperazine-1-carbonyl)benzaldehyde (810 mg, yield 80%) as a light yellow oil. 1H-NMR (400 MHz, CDCl3) δ (ppm): 0.79-0.85 (m, 2H), 1.00-1.04 (m, 2H), 1.72-1.80 (m, 1H), 3.41-3.81 (m, 8H), 7.58-7.60 (d, J=8.0 Hz, 1H), 7.95-7.97 (d, J=8.0 Hz, 1H), 10.07 (s, 1H); LC-MS (ESI) m/z: 287 (M+1)+.

Workup

  1. additionAfter the addition
  2. temperatureThen the mixture was cooled to 0° C.
  3. additionAfter the addition
  4. stirringto stir at room temperature overnight
  5. washwashed with saturated citric acid (100 mL×2)
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-c11ec5e38e2d46fcb0e95dc54eff41ce
Source dataset
uspto-grants-2015_04
Patent number
US08999987B2

Reaction notes

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