Hydrochloric Acid → HCID 66932348, compound

HRID 2046735Notes

Reaction equation

HRID 2046735 reaction equation
[OH-].[Na+].C[O:4][C:5](=[O:34])/[CH:6]=[CH:7]/[C:8]1[CH:9]=[C:10]2[C:30](=[CH:31][CH:32]=1)[O:29][C:13]1([CH2:18][CH2:17][N:16]([CH2:19][C:20]3[C:28]4[C:23](=[CH:24][CH:25]=[CH:26][CH:27]=4)[NH:22][CH:21]=3)[CH2:15][CH2:14]1)[CH2:12][C:11]2=[O:33].Cl>O1CCOCC1.O>[NH:22]1[C:23]2[C:28](=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:20]([CH2:19][N:16]2[CH2:17][CH2:18][C:13]3([CH2:12][C:11](=[O:33])[C:10]4[C:30](=[CH:31][CH:32]=[C:8](/[CH:7]=[CH:6]/[C:5]([OH:34])=[O:4])[CH:9]=4)[O:29]3)[CH2:14][CH2:15]2)=[CH:21]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 66932387HCID 66932387, compound

Product 1

HCID 66932348HCID 66932348, compound

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

4 M NaOH (0.081 ml, 0.325 mmol) was added to a solution of (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (140 mg, 0.325 mmol) in dioxane (2 ml) and water (1 ml) and the mixture was stirred at RT for 10 h. The pH was brought to 4 with 2 M HCl and the solvent was removed under vacuum to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid. The crude compound (135 mg) was dissolved in THF (12 ml). TEA (0.092 ml, 0.66 mmol), EDC (126 mg, 0.66 mmol) HOBT (44 mg, 0.33 mmol) and NH2OTHP (48 mg, 0.41 mmol) were added and the mixture was stirred at RT overnight. The solvent was removed and the residue was partitioned between DCM and water. The organic phase was dried over Na2SO4, evaporated and the crude product was purified by column chromatography (eluent:DCM/MeOH/NH4OH 96:4:0.4). The resulting (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide was dissolved in DCM and treated with HCl/Et2O for 3 h. The precipitate was filtered and washed with DCM to give (E)-3-{1′-(1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide hydrochloride as a white solid (40 mg).

Workup

  1. customthe solvent was removed under vacuum

Sources & evidence

ORD record
ord-f1af7da214ce46118bcd6e33efe9e1be
Source dataset
uspto-grants-2013_11
Patent number
US08592444B2

Reaction notes

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