Sodium Hydroxide → (2S)-2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-(4-fluorophenyl)-3-hydroxybut-1-ynyl)-3-methylnaphthalen-2-yl)acetic acid

HRID 926155Notes

Reaction equation

[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([C:23]#[C:24][C:25]([C:28]3[CH:33]=[CH:32][C:31]([F:34])=[CH:30][CH:29]=3)([OH:27])[CH3:26])=[CH:17][CH:18]=2)[C:13]=1[C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)[C:7]([O:9]CC)=[O:8])([CH3:4])([CH3:3])[CH3:2].[OH-].[Na+]>C1COCC1.CO.O>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([C:23]#[C:24][C:25]([C:28]3[CH:29]=[CH:30][C:31]([F:34])=[CH:32][CH:33]=3)([OH:27])[CH3:26])=[CH:17][CH:18]=2)[C:13]=1[C:35]1[CH:40]=[CH:39][C:38]([Cl:41])=[CH:37][CH:36]=1)[C:7]([OH:9])=[O:8])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 60 °C

Procedure

To a solution of (2S)-ethyl 2-tert-butoxy-2-(1-(4-chlorophenyl)-7-(3-(4-fluorophenyl)-3-hydroxybut-1-ynyl)-3-methylnaphthalen-2-yl)acetate (22 mg, 0.045 mmol) in 2:2:1 THF/MeOH/H2O (1 mL total) was added a NaOH solution (4 M, 0.2 mL). The reaction mixture was stirred at 60° C. for 2 h. The mixture was partially concentrated and diluted with MeCN and H2O and purified by reverse phase HPLC (MeCN/H2O) to give the titled compound. 1H-NMR: 400 MHz, (CD3OD) δ: 7.75 (d, J=8 Hz, 1H), 7.67 (m, 4H), 7.56 (m, 2H), 7.43 (m, 1H), 7.35 (s, 1H), 7.31 (d, J=8 Hz, 1H), 7.05 (m, 2H), 5.12 (s, 1H), 2.62 (s, 3H), 1.74 (s, 1H), 0.96 (s, 9H). LCMS-ESI+ (m/z): [M-OH]+ calcd for C33H29ClFO3: 527.2. Found: 527.2.

Workup

concentrationThe mixture was partially concentrated
additiondiluted with MeCN and H2O
custompurified by reverse phase HPLC (MeCN/H2O)

Sources & evidence

ORD record: ord-8d319ab08f6145ac86db530a8603701d
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284323B2

Reaction notes

Loading…