Methanamine, N-methoxy-, hydrochloride (1:1) → HCID 86697887, compound

HRID 338068Notes

Reaction equation

HRID 338068 reaction equation
[F:1][C:2]1[S:6][C:5]([C:7]([OH:9])=O)=[CH:4][CH:3]=1.Cl.[CH3:11][NH:12][O:13][CH3:14].O.ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(C(C)C)CC)(C)C>O1CCCC1.O>[F:1][C:2]1[S:6][C:5]([C:7]([N:12]([O:13][CH3:14])[CH3:11])=[O:9])=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 118049015-fluorothiophene-2-carboxylic acid

Product 1

HCID 86697887HCID 86697887, compoundYield 87.1%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-fluorothiophene-2-carboxylic acid (33.95 g, 232.3 mmol) in tetrahydrofuran (465 mL) at 0° C. under nitrogen is added N,O-dimethylhydroxylamine hydrochloride (45.32 g, 464.6 mmol), 1-hydroxybenzotriazole monohydrate (53.36 g, 348.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (89.1 g, 464.6 mmol), and diisopropylethylamine (162 mL, 929 mmol). The mixture is allowed to warm to room temperature over 18 hours. The mixture is diluted with water (500 mL) and extracted with ethyl acetate (500 mL). The aqueous phase is re-extracted twice with ethyl acetate (300 mL). The combined organic extracts are dried over sodium sulfate, filtered, and concentrated under reduced pressure. The liquid residue is purified by silica gel chromatography eluting with hexanes/ethyl acetate (3:1) to give the title compound (38.28 g, 87%) as a pale yellow liquid. ES/MS (m/e): 190 (M+H).

Workup

  1. extractionextracted with ethyl acetate (500 mL)
  2. extractionThe aqueous phase is re-extracted twice with ethyl acetate (300 mL)
  3. dry with materialThe combined organic extracts are dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe liquid residue is purified by silica gel chromatography
  7. washeluting with hexanes/ethyl acetate (3:1)

Sources & evidence

ORD record
ord-66830a8c6aa045618727cbf1a1d1b00b
Source dataset
uspto-grants-2014_11
Patent number
US08889856B2

Reaction notes

Loading…