Triethylamine → HCID 69950662, compound

HRID 382305Notes

Reaction equation

HRID 382305 reaction equation
[CH3:1][O:2][CH2:3][O:4][C@H:5]1[CH2:9][CH2:8][N:7]([CH2:10][C@H:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)O)[CH2:6]1.COCO[C@H]1CCN([C@H](C2C=CC=CC=2)CO)C1.C(N(CC)CC)C.CS(Cl)(=O)=O.[H-].[Na+].[Cl:51][C:52]1[CH:53]=[C:54]([CH:57]=[CH:58][C:59]=1[NH:60][CH3:61])[C:55]#[N:56].[NH4+].[OH-]>C(Cl)Cl.CN(C)C=O.O>[Cl:51][C:52]1[CH:53]=[C:54]([CH:57]=[CH:58][C:59]=1[N:60]([C@@H:11]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)[CH2:10][N:7]1[CH2:8][CH2:9][C@H:5]([O:4][CH2:3][O:2][CH3:1])[CH2:6]1)[CH3:61])[C:55]#[N:56]

Participants

11

Reactant 7

HCID 8471TriethylamineHCID 14923Ammonium HydroxideHCID 24758Sodium hydrideHCID 31297Methanesulfonyl chlorideHCID 15520998HCID 15520998, compoundHCID 15520999HCID 15520999, compoundHCID 159077543-Chloro-4-(methylamino)benzonitrile

Product 1

HCID 69950662HCID 69950662, compoundYield 61%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a stirred solution of the mixture of 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-1-(S)-phenylethanol and 2-(3-(S)-methoxymethoxypyrrolidin-1-yl)-2-(R)-phenylethanol (251 mg, 1.00 mmol) and triethylamine (0.167 ml, 1.20 mmol) in CH2Cl2 (4 ml) was added methanesulfonyl chloride (0.093 ml, 1.20 mmol) dropwise at 0° C. (ice bath). After 15.5 h stirring at room temperature, the reaction mixture was washed with saturated NaHCO3 aqueous solution, brine, dried (Na2SO4), and concentrated to give 238 mg of brown viscous oil-(i). To a suspension of NaH, (48 mg, 1.20 mmol) in N,N-dimethylformamide (2 ml) was added a solution of 3-chloro-4-methylaminobenzonitrile (200 mg, 1.20 mmol) at room temperature. After stirring for 45 min, to this mixture was added a solution of the above brown viscous oil-(i) in N,N-dimethylformamide (2 ml) at room temperature and the mixture was stirred at room temperature for 4.5 h. H2O was added to this mixture, basified with 25%-NH4OH, and extracted with CH2Cl2. The extract was washed with water, brine, dried (Na2SO4), and concentrated to give brown oil, which was purified by column chromatography (silica gel 20 g, CH2Cl2/MeOH 100/1-50/1) to afford 244 mg (61%) of brown oil.

Workup

  1. washthe reaction mixture was washed with saturated NaHCO3 aqueous solution, brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated
  4. customto give 238 mg of brown viscous oil-(i)
  5. stirringAfter stirring for 45 min, to this mixture
  6. stirringthe mixture was stirred at room temperature for 4.5 h
  7. extractionextracted with CH2Cl2
  8. washThe extract was washed with water, brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customto give brown oil, which
  12. customwas purified by column chromatography (silica gel 20 g, CH2Cl2/MeOH 100/1-50/1)

Sources & evidence

ORD record
ord-853183798ca24758a0327e3cc1a99b48
Source dataset
uspto-grants-2001_10
Patent number
US06310061B2

Reaction notes

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