Methanol → trans-2-({4'-[(5-Fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acid

HRID 9608Notes

Reaction equation

HRID 9608 reaction equation
[OH-].[Na+].[F:3][C:4]1[CH:5]=[CH:6][C:7]2[S:11][C:10]([NH:12][C:13]3[CH:18]=[CH:17][C:16]([C:19]4[CH:24]=[CH:23][C:22]([C:25]([C@@H:27]5[CH2:31][CH2:30][CH2:29][C@H:28]5[C:32]([O:34]C)=[O:33])=[O:26])=[CH:21][CH:20]=4)=[CH:15][CH:14]=3)=[N:9][C:8]=2[CH:36]=1.CO>C1COCC1>[F:3][C:4]1[CH:5]=[CH:6][C:7]2[S:11][C:10]([NH:12][C:13]3[CH:14]=[CH:15][C:16]([C:19]4[CH:24]=[CH:23][C:22]([C:25]([C@@H:27]5[CH2:31][CH2:30][CH2:29][C@H:28]5[C:32]([OH:34])=[O:33])=[O:26])=[CH:21][CH:20]=4)=[CH:17][CH:18]=3)=[N:9][C:8]=2[CH:36]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 11984509trans-Methyl 2-({4'-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentane-carboxylate

Product 1

HCID 11984466trans-2-({4'-[(5-Fluoro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclopentanecarboxylic acidYield 84%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

A solution of 1 N aqueous sodium hydroxide solution (1 mL) was added to trans-methyl 2-({4′-[(5-fluoro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclopentane-carboxylate (55 mg, 0.12 mmol) in THF (2 mL). Methanol was added until the mixture became homogeneous, and the resulting solution was heated at 60° C. for 1 h. The reaction was concentrated under reduced pressure to remove excess solvents, and the residue was partitioned between water and chloroform/isopropanol (4:1). The aqueous layer was adjusted to pH 2 by addition of aqueous phosphoric acid solution, with stirring. The organic layer was then separated, dried (Na2SO4), and concentrated under reduced pressure. The residue was suspended in acetone, and the resulting solid was collected by filtration and dried in vacuo to provide the title compound (45 mg, 84%). 1H NMR (300 MHz, acetone-d6) δ 10.40–10.10 (br s, 1 H), 8.15 (d, 2 H), 8.01 (d, 2 H), 7.87–7.82 (m, 5 H), 7.41 (dd, 1 H), 7.05–6.95 (m, 1 H), 4.26–4.17 (m, 1 H), 3.43–3.34 (m, 1 H), 2.31–2.23 (m, 1 H), 1.98–1.70 (m, 5 H); LC-MS m/z 461.3 (MH+), retention time 3.56 minutes.

Workup

  1. concentrationThe reaction was concentrated under reduced pressure
  2. customto remove excess solvents
  3. customthe residue was partitioned between water and chloroform/isopropanol (4:1)
  4. additionThe aqueous layer was adjusted to pH 2 by addition of aqueous phosphoric acid solution
  5. customThe organic layer was then separated
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated under reduced pressure
  8. filtrationthe resulting solid was collected by filtration
  9. customdried in vacuo

Sources & evidence

ORD record
ord-89e1b566444047c999b485ad57944331
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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