Methanol → HCID 2757206, compound

HRID 1698889Notes

Reaction equation

HRID 1698889 reaction equation
[C:1]([NH:8][C:9]1[CH:13]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[S:11][C:10]=1[C:18]([O:20]C)=[O:19])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1COCC1.CO.[OH-].[Na+]>O>[C:1]([NH:8][C:9]1[CH:13]=[C:12]([C:14]([CH3:17])([CH3:16])[CH3:15])[S:11][C:10]=1[C:18]([OH:20])=[O:19])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2]

Participants

6

Reactant 4

HCID 887MethanolHCID 8028TetrahydrofuranHCID 14798Sodium HydroxideHCID 18322389HCID 18322389, compound

Product 1

HCID 2757206HCID 2757206, compoundYield 65%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
60 °C

Procedure

To a solution of methyl 3-(N-carbo-tert-butoxyamino)-5-tert-butylthiophene-2-carboxylate (10.7 g, 34.1 mmol) in a 2:1:1 mixture of THF, MeOH and H2O (340 mL) was added NaOH (4.09 g, 102.3 mmol, 3.0 equiv). The resulting solution was heated at 60° C. for 18 h, cooled to room temp. and concentrated under reduced pressure. The residue was separated between H2O (500 mL) and EtOAc (250 mL). The aqueous phase was adjusted to pH 2 with a 10% HCl solution, then extracted with EtOAc (2×400 mL). The organic phase was washed with a saturated NaCl solution (250 mL), dried (MgSO4), and concentrated under reduced pressure to afford 3-(N-carbo-tert-butoxyamino)-5-tert-butylthiophene-2-carboxylic acid as an orange solid (6.6 g, 65%). This material was used in the next step without further purification. An analytical sample of the carboxylic acid was further purified: mp 187-8° C., TLC (10% MeOH/CH2Cl2) Rf0.17; 1H NMR (CDCl3) δ1.40 (s, 9H), 1.54 (s, 9H), 7.73 (s, 1H), 9.19 (s, 1H); 13C NMR (CDCl3) δ28.2 (3C), 31.8 (3C), 35.4, 81.3, 104.6, 116.7, 146.7, 151.9, 166.6, 169.3; FAB-LRMS m/z (rel abundance) 300 (M+H, 30%).

Workup

  1. temperaturecooled to room temp.
  2. concentrationconcentrated under reduced pressure
  3. customThe residue was separated between H2O (500 mL) and EtOAc (250 mL)
  4. extractionextracted with EtOAc (2×400 mL)
  5. washThe organic phase was washed with a saturated NaCl solution (250 mL)
  6. dry with materialdried (MgSO4)
  7. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-9318667726bd46c9b89b0762d0a903e8
Source dataset
uspto-grants-2002_02
Patent number
US06344476B1

Reaction notes

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