Sodium Hydroxide → (E)-3-{1'-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid

HRID 518237Notes

Reaction equation

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

Participants

Reactant 2

HCID 14798Sodium Hydroxide

HCID 66932473(E)-3-{1'-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acid methyl ester

Product 1

HCID 66932589(E)-3-{1'-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4'-piperidine]-6-yl}-acrylic acidYield 95%

Procedure

(E)-3-{1′-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (600 mg, 1.26 mmol) was treated with 1 M NaOH following the procedure described in Example 71 Step B, giving (E)-3-{1′-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid (548 mg, 95%). The resulting product was treated with NH2OTHP according to the procedure described in Example 71 Step C, giving (E)-3-{1′-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide. Finally, removal of the THP protecting group following the procedure described in Example 71 Step C gave (E)-3-{1′-(2-phenyl-thiazol-4-yl-methyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide hydrochloride (202 mg).

Sources & evidence

ORD record: ord-ff260349161349beb9b660e70eab8bde
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115148B2

Reaction notes

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