Sodium Hydroxide → 4-[[(1S,4S)-5-[[4-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoic acid

HRID 16535Notes

Reaction equation

HRID 16535 reaction equation
[F:1][C:2]([F:33])([CH:30]([F:32])[F:31])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][C@@H:16]3[CH2:18][C@H:13]2[CH2:14][N:15]3[CH2:19][C:20]2[CH:29]=[CH:28][C:23]([C:24]([O:26]C)=[O:25])=[CH:22][CH:21]=2)=[CH:7][CH:6]=1.[OH-].[Na+]>CO>[F:33][C:2]([F:1])([CH:30]([F:32])[F:31])[CH2:3][O:4][C:5]1[CH:10]=[CH:9][C:8]([CH2:11][N:12]2[CH2:17][C@@H:16]3[CH2:18][C@H:13]2[CH2:14][N:15]3[CH2:19][C:20]2[CH:29]=[CH:28][C:23]([C:24]([OH:26])=[O:25])=[CH:22][CH:21]=2)=[CH:7][CH:6]=1

Participants

4

Reactant 2

HCID 14798Sodium HydroxideHCID 86613444methyl 4-[[(1S,4S)-5-[[4-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate

Product 1

HCID 468990474-[[(1S,4S)-5-[[4-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoic acidYield 52.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Methyl 4-[[(1S,4S)-5-[[4-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoate (177 mg, 0.38 mmol) was stirred with 1.9 mL aqueous sodium hydroxide solution (2 M) in 3.9 mL methanol overnight at room temperature, and then concentrated under reduced pressure. The residue was diluted with water, adjusted to pH 8 with 1 M aqueous hydrochloric acid, and extracted with butanol. The combined organic layers were concentrated under reduced pressure. Flash chromatography gave 91 mg of 4-[[(1S,4S)-5-[[4-(2,2,3,3-tetrafluoropropoxy)phenyl]methyl]-2,5-diazabicyclo[2.2.1]hept-2-yl]methyl]benzoic acid; 1H NMR (300 MHz, CD3OD) δ 7.92 (d, 2H), 7.41 (d, 2H), 7.40 (d, 2H), 7.02 (d, 2H), 6.32 (tt, 1H), 4.45 (tt, 2H), 3.98 (d, 2H), 3.88 (d, 2H), 3.69 (br s, 1H), 3.64 (br s, 1H), 3.17 (d, 1H), 3.12 (d, 1H), 2.90 (dd, 1H), 2.85 (dd, 1H), 2.02 (s, 2H) ppm.

Workup

  1. concentrationconcentrated under reduced pressure
  2. additionThe residue was diluted with water
  3. extractionextracted with butanol
  4. concentrationThe combined organic layers were concentrated under reduced pressure

Sources & evidence

ORD record
ord-c59443b22e874fa395605a8477d5d731
Source dataset
uspto-grants-2010_06
Patent number
US07737145B2

Reaction notes

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