Sodium Hydroxide → HCID 66932568, compound

HRID 2046737Notes

Reaction equation

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

Participants

Reactant 2

HCID 14798Sodium Hydroxide

HCID 66932316HCID 66932316, compound

Product 1

HCID 66932568HCID 66932568, compoundYield 76%

Procedure

(E)-3-{1′-(6-Fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid methyl ester (130 mg, 0.29 mmol) was hydrolyzed with 4 M NaOH following the procedure described in Example 40, Step B, giving (E)-3-{1′-(6-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-acrylic acid as a yellow solid (95 mg, 76%). The product was treated with NH2OTHP according to the procedure described in Example 40, Step C, giving (E)-3-{1′-(6-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-(tetrahydro-pyran-2-yloxy)-acrylamide. Removal of the THP protecting group following the procedure described in Example 40, Step C gave (E)-3-{1′-(6-fluoro-1H-indol-3-ylmethyl)-4-oxo-spiro[chromane-2,4′-piperidine]-6-yl}-N-hydroxy-acrylamide that was purified by preparative LC-MS and obtained as its trifluoroacetate salt (15 mg, white solid).

Sources & evidence

ORD record: ord-2dcf5014b1de4e1f923030e9bd4b9860
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08592444B2

Reaction notes

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