Ethanolamine → HCID 69883411, compound

HRID 2120347Notes

Reaction equation

HRID 2120347 reaction equation
[CH2:1]([CH2:3][NH2:4])[OH:2].[Cl:5][C:6]1[C:11](F)=[C:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)(=[O:15])=[O:14])[CH:9]=[CH:8][C:7]=1[NH:23][C:24](=[O:32])[C@:25]([OH:31])([CH3:30])[C:26]([F:29])([F:28])[F:27]>CN1C(=O)CCC1.CO.C(Cl)Cl>[Cl:5][C:6]1[C:11]([NH:4][CH2:3][CH2:1][OH:2])=[C:10]([S:13]([C:16]2[CH:21]=[CH:20][C:19]([F:22])=[CH:18][CH:17]=2)(=[O:14])=[O:15])[CH:9]=[CH:8][C:7]=1[NH:23][C:24](=[O:32])[C@:25]([OH:31])([CH3:30])[C:26]([F:28])([F:29])[F:27]

Participants

5

Reactant 2

HCID 700EthanolamineHCID 86759332HCID 86759332, compound

Product 1

HCID 69883411HCID 69883411, compoundYield 33.9%

Reagents, catalysts & solvents 2

HCID 13387N-methyl-2-pyrrolidoneSolventHCID 21226129Dichloromethane methanolSolvent

Conditions

Temperature
120 °C

Procedure

Ethanolamine (47 mg, 2.5 eq) was added to a solution of (R)-N-(2-chloro-3-fluoro-4-{4-fluorophenylsulphonyl}phenyl)-2-hydroxy-2-methyl-3,3,3-trifluoropropanamide (Example 11) (135 mg) in NMP (1 ml) and the mixture was stirred and heated (oil bath 120° C.) under argon for 24 hours. The reaction mixture was cooled and partitioned between a saturated aqueous solution of ammonium chloride (10 ml) and ether (3×20 ml). The combined ether extracts were washed with water (50 ml), dried and concentrated to give a gum. The residue was dissolved in MeOH/DCM and loaded onto deactivated silica (1 g). It was then concentrated to give a free flowing powder which was poured onto an ISOLUTE column (10 g silica) and chromatographed eluting with EtOAc/isohexane to give the title compound (50 mg) as a gum. NMR: 1.65 (s, 3H), 3.2 (m, 2H), 3.42 (m, 2H), 4.92 (t, 1H), 5.91 (t, 1H), 7.47 (t, 2H), 7.89 (d, 1H), 7.96-8.08 (m, 3H), 9.85 (brs, 1H); m/z: 483.

Workup

  1. temperatureThe reaction mixture was cooled
  2. custompartitioned between a saturated aqueous solution of ammonium chloride (10 ml) and ether (3×20 ml)
  3. washThe combined ether extracts were washed with water (50 ml)
  4. customdried
  5. concentrationconcentrated
  6. customto give a gum
  7. concentrationIt was then concentrated
  8. customto give
  9. additionwas poured onto an ISOLUTE column (10 g silica)
  10. customchromatographed
  11. washeluting with EtOAc/isohexane

Sources & evidence

ORD record
ord-d414bc45ea38453b9265f68c04e5308b
Source dataset
uspto-grants-2004_02
Patent number
US06689909B1

Reaction notes

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