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

HRID 729386Notes

Reaction equation

HRID 729386 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-cb1e9e3032c6456d8ff658e4953fb462
Source dataset
uspto-grants-2009_09
Patent number
US07582627B2

Reaction notes

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