Acetaldehyde → HCID 66932625, compound
Reaction equation
[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:16][CH2:15][N:14]([C:17](OC(C)(C)C)=O)[CH2:13][CH2:12]1)[CH2:10][C:9]2=[O:28].[CH:30](=O)C.[Na]>C([O-])([O-])=O.[Na+].[Na+]>[CH3:1][O:2][C:3](=[O:29])/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:25](=[CH:26][CH:27]=1)[O:24][C:11]1([CH2:12][CH2:13][N:14]([CH2:17][CH3:30])[CH2:15][CH2:16]1)[CH2:10][C:9]2=[O:28]Participants
Procedure
A suspension of (E)-3-{4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (338 mg, 1.00 mmol, Intermediate 1, hydrochloride salt) in 1 M Na2CO3 was stirred for 10 minutes, then extracted with DCM and treated with acetaldehyde (88 mg, 2.0 mmol) and sodium triacethoxyborohydride (318 mg, 1.5 mmol) following the procedure described in Example 55, Step A, giving (E)-3-{1′-ethyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (200 mg) as a yellow oil. The ester was hydrolyzed as described in Example 55, Step B, giving (E)-3-{1′-ethyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (210 mg) as a white solid (hydrochloride salt). The resulting acid was suspended in DCM (7 ml), TEA (0.13 ml, 0.93 mmol) was added, and the resulting clear solution was treated with NH2OTHP following the procedure described in Example 1, Step B, giving (E)-3-{1′-ethyl-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide (180 mg) as a light yellow solid. The compound was dissolved in DCM (6 ml) and treated with 1 M HCl in diethyl ether (6 ml, 6 mmol) as described in Example 2, Step D, giving a light yellow solid (114 mg, hydrochloride salt)
Workup
- extractionextracted with DCM
Sources & evidence
- ORD record
- ord-2975beb1a20e438b81be04e293ffd8c7
- Source dataset
- uspto-grants-2013_11
- Patent number
- US08592444B2
Reaction notes
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