Hydrochloric Acid → Methyl 2-[(4'-amino-3'-fluoro-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylate

HRID 9553Notes

Reaction equation

HRID 9553 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([C:11]2[CH:16]=[CH:15][C:14]([C:17]([CH:19]3[CH2:23][CH2:22][CH2:21][CH:20]3[C:24]([O:26][CH3:27])=[O:25])=[O:18])=[CH:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[NH:8]C=O.Cl>CO>[NH2:8][C:7]1[CH:6]=[CH:5][C:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17]([CH:19]3[CH2:23][CH2:22][CH2:21][CH:20]3[C:24]([O:26][CH3:27])=[O:25])=[O:18])=[CH:15][CH:16]=2)=[CH:3][C:2]=1[F:1]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 21985795Methyl 2-{[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]carbonyl}cyclopentanecarboxylate

Product 1

HCID 21985843Methyl 2-[(4'-amino-3'-fluoro-1,1'-biphenyl-4-yl)carbonyl]cyclopentanecarboxylateYield 89.3%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of methyl 2-{[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-carbonyl}cyclopentanecarboxylate (4.24 g, 11.48 mmol) in methanol (34 mL) was added conc. HCl (11.4 mL), and the resulting solution was stirred at rt for 2 h. Solvent was then removed, the residual mixture was dissolved in water, and the acidity of the mixture was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution. The mixture was then extracted with dichloromethane and washed with saturated sodium chloride solution, dried over sodium sulfate, and the solvent was removed in vacuo. The crude mixture was then triturated with ethyl acetate/hexane to afford methyl 2-[(4′-amino-3′-fluoro-1,1′-biphenyl-4-yl)carbonyl]cyclopentane-carboxylate (3.5 g, 89%, 80% ee). LC-MS ret. time 3.00 min, m/z 370.0 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.52–1.84 (m, 4H), 1.97–2.02 (m, 1H), 2.14–2.18 (m, 1H), 3.24–3.33 (m, 1H), 3.56 (s, 3H), 4.08 (q, 1H), 5.47 (br s, 2H), 6.84 (t, 1H), 7.34 (dd, 1H), 7.48 (dd, 1H), 7.78 (d, 2H), 7.99 (d, 2H).

Workup

  1. customSolvent was then removed
  2. dissolutionthe residual mixture was dissolved in water
  3. additionthe acidity of the mixture was adjusted to pH ˜7 by slow addition of saturated aqueous sodium bicarbonate solution
  4. extractionThe mixture was then extracted with dichloromethane
  5. washwashed with saturated sodium chloride solution
  6. dry with materialdried over sodium sulfate
  7. customthe solvent was removed in vacuo
  8. customThe crude mixture was then triturated with ethyl acetate/hexane

Sources & evidence

ORD record
ord-8d36461a5b9b4aaf9debfc514fc25769
Source dataset
uspto-grants-2006_08
Patent number
US07091228B2

Reaction notes

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