Sodium Hydroxide → trans-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexanecarboxylic acid

HRID 9618Notes

Reaction equation

HRID 9618 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][C:11]([C:14]([C@H:16]3[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]3[C:22]([O:24]C)=[O:23])=[O:15])=[CH:10][CH:9]=2)=[CH:4][CH:3]=1.Cl[C:27]1[S:28][C:29]2[CH:35]=[C:34]([Cl:36])[CH:33]=[CH:32][C:30]=2[N:31]=1.[OH-].[Na+]>C(O)CCC>[Cl:36][C:34]1[CH:33]=[CH:32][C:30]2[N:31]=[C:27]([NH:1][C:2]3[CH:3]=[CH:4][C:5]([C:8]4[CH:13]=[CH:12][C:11]([C:14]([C@@H:16]5[CH2:21][CH2:20][CH2:19][CH2:18][C@H:17]5[C:22]([OH:24])=[O:23])=[O:15])=[CH:10][CH:9]=4)=[CH:6][CH:7]=3)[S:28][C:29]=2[CH:35]=1

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 771762,6-DichlorobenzothiazoleHCID 67147298Methyl cis-2-[(4'-amino-1,1'-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate

Product 1

HCID 11584016trans-2-({4'-[(6-Chloro-1,3-benzothiazol-2-yl)amino]-1,1'-biphenyl-4-yl}carbonyl)cyclohexanecarboxylic acidYield 15.5%

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of cis-methyl 2-[(4′-amino-1,1′-biphenyl-4-yl)carbonyl]cyclohexanecarboxylate (200 mg, 0.59 mmol) in n-butanol (8 mL) was added 2,6-dichloro-1,3-benzothiazole (241 mg, 1.19 mmol), and the resulting reaction mixture was heated at 90° C. overnight. The mixture was evaporated to dryness and the residue was combined with MeOH. Then 1 N NaOH (6.0 mL, 6.0 mmol) was added to the suspension, and the reaction mixture was stirred at 50° C. overnight. The reaction mixture was concentrated under reduced pressure, and the residue was suspended in water. Concentrated aqueous HCl was added to adjust the acidity to pH 1, and the precipitate was collected by filtration, washed with water and MeOH, and dried in a vacuum oven to give trans-2-({4′-[(6-chloro-1,3-benzothiazol-2-yl)amino]-1,1′-biphenyl-4-yl}carbonyl)cyclohexanecarboxylic acid (45 mg, 15%). LC-MS m/z 491.1 (MH+), ret. time 3.90 min; 1H NMR (400 MHz, DMSO-d6) δ 1.13 (m, 1H), 1.28˜1.51 (m, 3H), 1.78 (m, 1H), 1.93 (m, 1H), 2.09 (m, 1H), 2.68 (m, 1H), 3.63 (m, 1H), 7.35 (m, 1H), 7.60 (m, 1H), 7.80 (m, 4H), 7.90 (d, 1H), 7.96 (m, 1H), 8.05 (d, 2H), 10.75 (s, 1H).

Workup

  1. customthe resulting reaction mixture
  2. customThe mixture was evaporated to dryness
  3. concentrationThe reaction mixture was concentrated under reduced pressure
  4. additionConcentrated aqueous HCl was added
  5. filtrationthe precipitate was collected by filtration
  6. washwashed with water and MeOH
  7. customdried in a vacuum oven

Sources & evidence

ORD record
ord-00bd96e732804164bae07121e61b8ef7
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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