Ethyl Acetate → HCID 59553098, compound

HRID 1641281Notes

Reaction equation

HRID 1641281 reaction equation
Cl[CH2:2][CH2:3][O:4][C:5]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[C:8]([NH:15][C:16](=[O:30])[C:17]2[CH:22]=[C:21]([N:23]3[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]3)[CH:20]=[C:19]([F:29])[CH:18]=2)=[CH:7][CH:6]=1.[OH:31][CH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1.C(OCC)(=O)C>CC(C)=O.CS(C)=O>[F:29][C:19]1[CH:18]=[C:17]([CH:22]=[C:21]([N:23]2[CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]2)[CH:20]=1)[C:16]([NH:15][C:8]1[C:9]2[C:14](=[CH:13][CH:12]=[CH:11][CH:10]=2)[C:5]([O:4][CH2:3][CH2:2][N:35]2[CH2:36][CH2:37][CH:32]([OH:31])[CH2:33][CH2:34]2)=[CH:6][CH:7]=1)=[O:30]

Participants

6

Reactant 3

HCID 8857Ethyl AcetateHCID 79341Piperidin-4-olHCID 59553352HCID 59553352, compound

Product 1

HCID 59553098HCID 59553098, compoundYield 14.8%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 679Dimethyl SulfoxideSolvent

Procedure

N-[4-(2-Chloroethoxy)-naphthalen-1-yl]-3-fluoro-5-piperidin-1-yl-benzamide (100 mg, 234 mmol) and 4-hydroxypiperidine (118 mg, 1.17 mmol) in acetone (3 ml) and dimethylsulfoxide (1 ml) are heated to 180° C. with microwave irradiation for 20 min. After cooling to room temperature the mixture is poured into ethyl acetate (100 ml) and washed with water (100 ml). The organic layer is dried over anhydrous sodium sulfate and evaporated to dryness. The residue is purified by column chromatography on silica gel eluted with ethyl acetate followed by 10% methanol in dichloromethane to give 3-fluoro-N-{4-[2-(4-hydroxypiperidin-1-yl)-ethoxy]-naphthalen-1-yl}-5-piperidin-1-yl-benzamide as a colorless foam (85 mg). 1H NMR 300 MHz (CDCl3) 8.31(dd, 1H, J=1.8 and 8.4 Hz), 7.9(s, 1H), 7.83(d, 1H, J=7.2 Hz), 7.71(d, 1H, J=8.4 Hz), 7.53(m, 2H), 7.31(s, 1H), 6.98(d, 1H, J=9 Hz), 6.83(d, 1H, J=8.4 Hz), 6.76(d, 1H, J=12.3 Hz), 4.23(t, 2H, J=5.7 Hz), 3.74(m, 1H), 3.01(s, 4H), 2.98(m, 4H), 2.42(t, 2H, J=9.5 Hz), 1.95(m, 2H), 1.57-1.71(m, 8H).

Workup

  1. washwashed with water (100 ml)
  2. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  3. customevaporated to dryness
  4. customThe residue is purified by column chromatography on silica gel
  5. washeluted with ethyl acetate

Sources & evidence

ORD record
ord-a9438b5318d842be8c066fd259609254
Source dataset
uspto-grants-2012_02
Patent number
US08114873B2

Reaction notes

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