Methylamine → 3-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)propyl N-Methylcarbamate

HRID 748763Notes

Reaction equation

HRID 748763 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH:11]([C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[F:22])[CH2:12][CH2:13][OH:14])(=[O:10])=[O:9])=[CH:4][CH:3]=1.[CH2:23]([N:25]([CH2:28]C)CC)C.ClC(OC1C=CC([N+]([O-])=O)=CC=1)=[O:32].CN>ClCCl.CCCCCC.O1CCCC1>[CH3:23][NH:25][C:28](=[O:32])[O:14][CH2:13][CH2:12][CH:11]([S:8]([C:5]1[CH:4]=[CH:3][C:2]([Cl:1])=[CH:7][CH:6]=1)(=[O:10])=[O:9])[C:15]1[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=1[F:22]

Participants

8

Reactant 4

HCID 6329Methylamine2×HCID 8471TriethylamineHCID 821294-Nitrophenyl chloroformateHCID 230287923-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanol

Product 1

HCID 597508003-[(4-Chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)propyl N-MethylcarbamateYield 27%

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolvent2×HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolvent

Procedure

The 3-[(4-chlorophenyl)sulfonyl]-3-(2,5-difluorophenyl)-1-propanol (200 mg, 0.576 mmol) obtained in Example 207 was dissolved in dichloromethane (4 ml), followed by the addition, of triethylamine (84.2 μl, 0.605 mmol) and 4-nitrophenyl chloroformate (122 mg, 0.605 mmol). The resulting mixture was stirred at room temperature for 15 hours. After addition of methylamine (a 2.00M tetrahydrofuran solution, 2.0 ml, 4.00 mmol), the mixture was stirred at room temperature for 24 hours. Methylamine (a 2.00M tetrahydrofuran solution, 3.0 ml, 4.00 mmol) was added and the mixture was stirred at room temperature for 5 hours. The reaction mixture was diluted with dichloromethane, washed successively with a saturated aqueous solution of sodium bicarbonate, water and brine, dried over magnesium sulfate and then, concentrated. The residue thus obtained was subjected to flash chromatography on a silica gel column, and the fraction obtained from the hexane:ethyl acetate=3:2 eluate was concentrated. The concentrate was purified further by high performance liquid chromatography (using a mixed solvent of water/acetonitrile/formic acid) to yield the title compound (62.1 mg, 0.154 mmol, 27%) as a colorless oil.

Workup

  1. stirringwas stirred at room temperature for 24 hours
  2. stirringthe mixture was stirred at room temperature for 5 hours
  3. washwashed successively with a saturated aqueous solution of sodium bicarbonate, water and brine
  4. dry with materialdried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue thus obtained
  7. concentrationethyl acetate=3:2 eluate was concentrated
  8. customThe concentrate was purified further by high performance liquid chromatography (

Sources & evidence

ORD record
ord-f4b81cba8325455db702e065d3881d75
Source dataset
uspto-grants-2008_07
Patent number
US07399775B2

Reaction notes

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