Triethylamine → HCID 86672380, compound

HRID 1047507Notes

Reaction equation

HRID 1047507 reaction equation
Br[CH2:2][CH2:3][CH2:4][O:5][CH2:6][C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.N[CH2:14][CH2:15][CH2:16][OH:17].[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([S:25]([C:28]2[C:37]3[C:32](=[C:33]([F:39])[CH:34]=[CH:35][C:36]=3[F:38])[O:31][CH2:30][CH:29]=2)(=[O:27])=[O:26])=[CH:21][CH:20]=1.C([N:42](CC)CC)C>C1COCC1>[CH2:6]([O:5][CH2:4][CH2:3][CH2:2][N:42]([CH:16]([OH:17])[CH2:15][CH3:14])[CH:29]1[CH:28]([S:25]([C:22]2[CH:21]=[CH:20][C:19]([Cl:18])=[CH:24][CH:23]=2)(=[O:26])=[O:27])[C:37]2[C:32](=[C:33]([F:39])[CH:34]=[CH:35][C:36]=2[F:38])[O:31][CH2:30]1)[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 90863-Amino-1-propanolHCID 2776064Benzyl 3-Bromopropyl EtherHCID 582522424-((4-Chlorophenyl)sulfonyl)-5,8-difluoro-2H-chromene

Product 1

HCID 86672380HCID 86672380, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Benzyl 3-bromopropyl ether (7.8475 g, 34.27 mmol) was dissolved in 50 ml of THF then 3-aminopropanol (2.56 g, 34.13 mmol) was added the reaction was stirred at room temperature for three days. The reaction was quenched with 100 ml of Sat. potassium carbonate solution and the solution was washed with ethyl acetate. The organic layer washed with Sat. potassium carbonate solution (2×100 mL) then dried over sodium sulfate and concentrated. This amine solution was used without any further purification. The amine solution (3.91 g, 17.5 mmol) was dissolved in 100 ml of THF. 4-(4-Chloro-benzenesulfonyl)-5,8-difluoro-2H-chromene (2.0486 g, 5.97 mmol) was added and the reaction was stirred at room temperature overnight. Triethylamine (3 ml) was added and the reaction was stirred at room temperature for 2 h. Then additional amine solution (2.85 g, 12.8 mmol) was added and the reaction was stirred overnight at room temperature then warmed to reflux and stirred overnight. The reaction was quenched with water (100 ml) and washed with ethyl acetate (100 ml). The organic layer was dried over sodium sulfate and concentrated. The product was purified by column using EtOAc/Hex. as the eluent (gradient from 0/100 to 100/0 in 45 minutes). Yield: 570 mg, 17%. 1H NMR (CDCl3 400 MHz) δ7.64-7.59 (m, 2H), 7.45-7.40 (m, 2H), 7.36-7.25 (m, 5H), 7.00 (td, J=9.5, 5.1 Hz, 1H), 6.42 (td, J=8.8, 3.7 Hz, 1H), 4.74 (dd, J=12.4, 5.1 Hz, 1H), 4.65 (s, 1H), 4.42 (s, 2H), 4.32-4.26 (m, 1H), 4.06-4.01 (m, 1H), 3.59 (t, J=5.4 Hz, 2H), 3.41 (t, J=5.9 Hz, 2H), 2.87 (bs, 1H), 2.71-2.53 (m, 3H), 2.50-2.42 (m, 1H), 1.74-1.62 (m, 3H), 1.60-1.50 (m, 1H).

Workup

  1. customThe reaction was quenched with 100 ml of Sat. potassium carbonate solution
  2. washthe solution was washed with ethyl acetate
  3. washThe organic layer washed with Sat. potassium carbonate solution (2×100 mL)
  4. dry with materialthen dried over sodium sulfate
  5. concentrationconcentrated
  6. customThis amine solution was used without any further purification
  7. stirringthe reaction was stirred at room temperature overnight
  8. stirringthe reaction was stirred at room temperature for 2 h
  9. stirringthe reaction was stirred overnight at room temperature
  10. temperaturethen warmed
  11. temperatureto reflux
  12. stirringstirred overnight
  13. customThe reaction was quenched with water (100 ml)
  14. washwashed with ethyl acetate (100 ml)
  15. dry with materialThe organic layer was dried over sodium sulfate
  16. concentrationconcentrated
  17. customThe product was purified by column
  18. customas the eluent (gradient from 0/100 to 100/0 in 45 minutes)

Sources & evidence

ORD record
ord-85049a9e745740f784d8ae317c1e4b68
Source dataset
uspto-grants-2013_10
Patent number
US08569521B2

Reaction notes

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