Hydrochloric Acid → HCID 66932348, compound

HRID 518199Notes

Reaction equation

HRID 518199 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-630a3622558942b28948ecbe01957732
Source dataset
uspto-grants-2015_08
Patent number
US09115148B2

Reaction notes

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