Acetic Acid → HCID 67071598, compound

HRID 874272Notes

Reaction equation

HRID 874272 reaction equation
C[O:2][C:3](=[O:28])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:24](=[CH:25][CH:26]=1)[O:23][C:11]1([CH2:17][CH2:16][CH2:15][N:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:27].Cl.CC(O)=O>C(Cl)Cl.CO>[CH2:21]([O:20][C:18]([N:14]1[CH2:15][CH2:16][CH2:17][C:11]2([CH2:10][C:9](=[O:27])[C:8]3[C:24](=[CH:25][CH:26]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:28])=[O:2])[CH:7]=3)[O:23]2)[CH2:12][CH2:13]1)=[O:19])[CH3:22]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 313Hydrochloric AcidHCID 67071609HCID 67071609, compound

Product 1

HCID 67071598HCID 67071598, compound

Reagents, catalysts & solvents 1

HCID 21226129Dichloromethane methanolSolvent

Procedure

(±)-(E)-3-[1′-Ethyloxycarbonyl-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid methyl ester was obtained starting from the hydrochloride salt of (±)-(E)-3-[4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid methyl ester (500 mg, 1.43 mmol, Intermediate 3) and ethyl chloro formate (0.163 ml, 1.70 mmol), according to the procedure described in Example 24, Step A, giving a yellow solid (540 mg, 97%). (±)-(E)-3-[1′-Ethyloxycarbonyl-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid methyl ester (530 mg, 1.37 mmol) was hydrolyzed using HCl and AcOH following the procedure described in Example 22, Step A. (±)-(E)-3-[1′-ethyloxycarbonyl-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid was obtained after column chromatography (eluent DCM/MeOH 9:1) as a white solid (101 mg, 21%). Hydrolysis of the carbamate function was not observed. The acrylic acid (100 mg, 0.26 mmol) was then treated with NH2OTHP according to the procedure described in Example 22, Step C, giving (E)-3-[1′-ethyloxycarbonyl-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (82 mg, 65%). Finally, removal of THP protecting group following the procedure described in Example 22, Step D gave (±)-(E)-3-[1′ethyloxycarbonyl-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-N-hydroxy-acrylamide (12.8 mg) as a light yellow solid.

Sources & evidence

ORD record
ord-feabb1c2b3294b2c9a3229489ffefb3e
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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