Methanol → 4-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2-cyclopropylamino-3-fluorobenzoic acid

HRID 10299Notes

Reaction equation

HRID 10299 reaction equation
C([O:3][C:4](=[O:30])[C:5]1[CH:10]=[C:9]([Cl:11])[C:8]([N:12]2[CH2:16][CH2:15][CH:14]([NH:17][C:18]([O:20][C:21]([CH3:24])([CH3:23])[CH3:22])=[O:19])[CH2:13]2)=[C:7]([F:25])[C:6]=1[NH:26][CH:27]1[CH2:29][CH2:28]1)C.[OH-].[Na+].CO>O1CCCC1>[C:21]([O:20][C:18]([NH:17][CH:14]1[CH2:15][CH2:16][N:12]([C:8]2[C:9]([Cl:11])=[CH:10][C:5]([C:4]([OH:30])=[O:3])=[C:6]([NH:26][CH:27]3[CH2:28][CH2:29]3)[C:7]=2[F:25])[CH2:13]1)=[O:19])([CH3:24])([CH3:22])[CH3:23]

Participants

5

Reactant 3

HCID 887MethanolHCID 14798Sodium HydroxideHCID 21041183HCID 21041183, compound

Product 1

HCID 219793744-[3-(tert-Butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2-cyclopropylamino-3-fluorobenzoic acidYield 91.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 4-[3-(tert-butoxycarbonylamino)pyrrolidin-1-yl]-5-chloro-2-cyclopropylamino-3-fluorobenzoic acid ethyl ester (Example 3k, 2.00 g, 4.50 mmol) and aqueous sodium hydroxide (2.0N, 20 mL) in tetrahydrofuran (20 mL), and methanol (20 mL) is refluxed for 1 hour. The solution is partially concentrated in vacuo, acidified to pH 6, and extracted with chloroform. The combined organic extracts are dried over Na2SO4, filtered, and concentrated to give the title compound (1.70 g). 1H NMR (CDCl3): δ 7.71 (d, 1H), 4.91–4.82 (bd, 1H), 4.40–4.25 (m, 1H), 3.77–3.69 (m, 2H), 3.53–3.34 (m, 2H), 3.00–2.88 (m, 1H), 2.24–2.15 (m, 1H), 1.90–1.80 (m, 1H), 1.46 (s, 9H), 0.72–0.54 (m, 4H).

Workup

  1. concentrationThe solution is partially concentrated in vacuo
  2. extractionextracted with chloroform
  3. dry with materialThe combined organic extracts are dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-a7f356a059ad4e31955c0bb42ee06496
Source dataset
uspto-grants-2006_08
Patent number
US07094780B1

Reaction notes

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