Sodium Hydroxide → 4-(4-tert-Butoxycarbonyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid

HRID 1643579Notes

Reaction equation

[OH-].[Na+].C[O:4][C:5]([C:7]1[CH:17]=[C:16]([O:18][C:19]2[CH:24]=[CH:23][C:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])=[C:21]([F:32])[CH:20]=2)[C:10]2[CH2:11][C:12]([CH3:15])([CH3:14])[O:13][C:9]=2[CH:8]=1)=[O:6]>CO>[C:28]([O:27][C:25]([C:22]1[CH:23]=[CH:24][C:19]([O:18][C:16]2[C:10]3[CH2:11][C:12]([CH3:15])([CH3:14])[O:13][C:9]=3[CH:8]=[C:7]([C:5]([OH:6])=[O:4])[CH:17]=2)=[CH:20][C:21]=1[F:32])=[O:26])([CH3:29])([CH3:30])[CH3:31]

Participants

Conditions

Temperature: 60 °C

Procedure

NaOH (6.20 mL, 19.0 mmol, 3N aqueous solution) was added to a solution of 4-(4-tert-butoxycarbonyl-3-fluoro-phenoxy)-2,2-dimethyl-2,3-dihydro-benzofuran-6-carboxylic acid methyl ester (66a) (2.56 g, 5.91 mmol) in 30 mL MeOH. The reaction mixture was heated to 60° C. for 2 hr, concentrated, diluted with H2O (100 mL), acidified with 1N aqueous HCl to Ph ˜1, and extracted with CH2Cl2 (2×100 mL). The combined organic layer was dried over MgSO4, concentrated in vacuo to give a white solid (2.46 g, 98% yield). 1H NMR (400 MHz, DMSO-d6) δ 13.08 (br. s., 1 H) 7.85 (t, J=8.72 Hz, 1 H) 7.11 (d, J=1.26 Hz, 1 H) 7.06 (d, J=1.01 Hz, 1 H) 6.99 (dd, J=12.13, 2.27 Hz, 1 H) 6.89 (dd, J=8.72, 2.40 Hz, 1 H) 2.87 (s, 2 H) 1.53 (s, 9H) 1.42 (s, 6 H); LCMS for C22H23FO6m/z 425.00 (M+Na)+.

Workup

concentrationconcentrated
additiondiluted with H2O (100 mL)
extractionextracted with CH2Cl2 (2×100 mL)
dry with materialThe combined organic layer was dried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-8b2318fe68e14725a68b967aee2689da
Source dataset: uspto-grants-2012_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08119624B2

Reaction notes

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