2-Dimethylaminopyridine → HCID 57546235, compound

HRID 913935

Reaction equation

HRID 913935 reaction equation
[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:8]([Cl:14])=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[F:15][C:16]1[CH:21]=[CH:20][C:19]([C:22]2([CH2:35]O)[CH2:27][CH2:26][N:25]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:24][CH2:23]2)=[CH:18][CH:17]=1.CN(C1C=CC=CN=1)C.Cl.C(N=C=NCCCN(C)C)C>ClCCl.C(OCC)C.O>[NH2:1][C:2]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][C:8]([Cl:14])=[CH:7][C:3]=1[C:4]([O:6][CH2:35][C:22]1([C:19]2[CH:20]=[CH:21][C:16]([F:15])=[CH:17][CH:18]=2)[CH2:23][CH2:24][N:25]([C:28]([O:30][C:31]([CH3:32])([CH3:33])[CH3:34])=[O:29])[CH2:26][CH2:27]1)=[O:5]

Participants

8

Reactant 4

HCID 218852-DimethylaminopyridineHCID 2320552-Amino-5-chloro-3-nitrobenzoic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 19084679Tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate

Product 1

HCID 57546235HCID 57546235, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-amino-5-chloro-3-nitrobenzoic acid (500 mg, 2.3 mmol), tert-butyl 4-(4-fluorophenyl)-4-(hydroxymethyl)piperidine-1-carboxylate (714 mg, 2.3 mmol), and dimethylaminopyridine (282 mg, 2.3 mmol) in dichloromethane (6.6 mL) was added 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (664 mg, 3.46 mmol) in one portion. The suspension was stirred overnight. The reaction was poured into water and diluted with diethyl ether. The ethereal was washed with water, then saturated sodium bicarbonate, then water. The ethereal was washed with brine, dried over magnesium sulfate, and concentrated. Column chromatography (15%→30% ethyl acetate/n-hexane) gave 0.88 g (75%) as a yellow foam solid. 1H-NMR (CDCl3, 500 MHz) δ 8.31 (d, J=2.4 Hz, 1H), 8.27 (bs, 2H), 7.87 (d, J=2.8 Hz, 1H), 7.36 (dd, J=8.9, 5.2 Hz, 2H), 7.09 (dd, J=8.9, 8.6 Hz, 2H), 4.25 (s, 2H), 3.81 (m, 2H), 3.06 (m, 2H), 2.25 (m, 2H), 1.86 (m, 2H), 1.43 (s, 9H); 13C NMR (126 MHz, CDCl3) δ ppm 165.5, 161.8 (d, J=248 Hz), 154.9, 145.8, 138.6, 136.8, 133.5, 131.6, 128.8 (d, J=7.7 Hz), 118.9, 115.8 (d, J=21 Hz), 115.4, 79.8, 73.2, 40.8, 39.9, 32.2, 28.5.

Workup

  1. washThe ethereal was washed with water
  2. washThe ethereal was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated
  5. customColumn chromatography (15%→30% ethyl acetate/n-hexane) gave 0.88 g (75%) as a yellow foam solid

Sources & evidence

ORD record
ord-c8fb5b4bfece42dfa5179180b948b099
Source dataset
uspto-grants-2011_09
Patent number
US08026257B2

Linked notes

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