Hydrochloric Acid → HCID 67071385, compound

HRID 874273Notes

Reaction equation

HRID 874273 reaction equation
C[O:2][C:3](=[O:31])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:27](=[CH:28][CH:29]=1)[O:26][C:11]1([CH2:17][CH2:16][CH2:15][N:14]([CH2:18][CH2:19][C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:30].Cl>CC(O)=O>[C:20]1([CH2:19][CH2:18][N:14]2[CH2:15][CH2:16][CH2:17][C:11]3([CH2:10][C:9](=[O:30])[C:8]4[C:27](=[CH:28][CH:29]=[C:6](/[CH:5]=[CH:4]/[C:3]([OH:31])=[O:2])[CH:7]=4)[O:26]3)[CH2:12][CH2:13]2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 67071757HCID 67071757, compound

Product 1

HCID 67071385HCID 67071385, compoundYield 101.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

(±)-(E)-3-[1′-(2-Phenyl-ethyl)-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 (1 g, 2.85 mmol, Intermediate 3) and phenethyl bromide (0.846 ml, 6.27 mmol), according to the procedure described in Example 24, Step A. The reaction was carried out for 15 days at RT and the methyl ester was obtained as a yellow solid (203 mg, 17%). (±)-(E)-3-[1′-(2-Phenyl-ethyl)-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid methyl ester (200 mg, 0.48 mmol) was hydrolyzed with HCl and AcOH following the procedure described in Example 22, Step A, giving (±)-(E)-3-[1′-(2-phenyl-ethyl)-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-acrylic acid as a white solid (197 mg, 93%). The acid was treated with NH2OTHP according to the procedure described in Example 22, Step C, giving (E)-3-[1′(2-phenyl-ethyl)-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]-N-(tetrahydro-pyran-2-yloxy)-acrylamide (183 mg, 83%). Finally, removal of THP protecting group following the procedure described in Example 22, Step D and purification using preparative HPLC gave (±)-(E)-3-[1′-(2-phenyl-ethyl)-4-oxo-spiro(chromane-2,4′-azepane)-6-yl]N-hydroxy-acrylamide (77.5 mg, 40%) as its trifluoroacetate salt.

Sources & evidence

ORD record
ord-3489cceb010c4ebe8d23c7c8acb93be3
Source dataset
uspto-grants-2015_03
Patent number
US08980877B2

Reaction notes

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