Lithium Hydroxide → HCID 66631107, compound

HRID 931833Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:25]2[CH2:32][CH2:31][C:28]3([CH2:30][CH2:29]3)[CH2:27][CH:26]=2)=[C:13]2[C:18](=[CH:19][C:20]=1[CH3:21])[N:17]=[C:16]([CH:22]([F:24])[F:23])[CH:15]=[CH:14]2)[C:7]([O:9]C)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Li+]>O1CCCC1.CO.O.C(#N)C>[C:1]([O:5][C@@H:6]([C:11]1[C:12]([C:25]2[CH2:32][CH2:31][C:28]3([CH2:29][CH2:30]3)[CH2:27][CH:26]=2)=[C:13]2[C:18](=[CH:19][C:20]=1[CH3:21])[N:17]=[C:16]([CH:22]([F:23])[F:24])[CH:15]=[CH:14]2)[C:7]([OH:9])=[O:8])([CH3:4])([CH3:2])[CH3:3]

Participants

Conditions

Temperature: 50 °C

Procedure

To a solution of (S)-methyl 2-tert-butoxy-2-(2-(difluoromethyl)-7-methyl-5-(spiro[2.5]oct-5-en-6-yl)quinolin-6-yl)acetate (44.7 mg, 0.101 mmol) in tetrahydrofuran:methanol:water (2:2:1, 2 mL) was added lithium hydroxide (12 mg, 0.504 mmol) and the reaction was heated to 50° C. overnight. The reaction was diluted with acetonitrile and purified by reverse phase HPLC (Gemini, 15 to 95 ACN/H2O+0.1% TFA) and the desired product was lyophilized to give a white powder (29.2 mg). 1H-NMR: 400 MHz, (CD3CN) δ: 8.49 (d, J=8.8 Hz, 1 H), 7.85 (s, 1 H), 7.69 (d, J=8.4 Hz, 1 H), 6.84 (t, =55.2 Hz, 1 H), 5.93 (s, 1 H), 5.68 (s, 1 H), 2.67 (m, 1 H), 2.62 (s, 3 H), 2.46 (m, 1 H), 2.28-2.24 (m, 2 H), 1.66 (m, 2 H), 1.23 (s, 9 H), 0.54-0.40 (m, 4 H). LCMS-ESI+ (m/z): [M+H]+ calcd for C25H30F2NO3: 430.21. found: 430.32.

Workup

custompurified by reverse phase HPLC (Gemini, 15 to 95 ACN/H2O+0.1% TFA)

Sources & evidence

ORD record: ord-6b463cbcc8fb4095a31265fb3ab96768
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09296758B2

Reaction notes

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