Dimethylamine → HCID 24984263, compound

HRID 1724071Notes

Reaction equation

HRID 1724071 reaction equation
O[CH2:2][CH2:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]3[CH2:23][C:22]4([CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[O:21][C:20]3=[O:29])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1.[CH2:30]([N:32](CC)[CH2:33]C)C.CS(Cl)(=O)=O.CNC>C(Cl)Cl>[CH3:30][N:32]([CH3:33])[CH2:2][CH2:3][O:4][CH2:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[CH:17]=[CH:16][C:15]([CH2:18][N:19]3[CH2:23][C:22]4([CH2:28][CH2:27][CH2:26][CH2:25][CH2:24]4)[O:21][C:20]3=[O:29])=[CH:14][CH:13]=2)=[CH:8][CH:7]=1

Participants

6

Reactant 4

HCID 674DimethylamineHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 24984262HCID 24984262, compound

Product 1

HCID 24984263HCID 24984263, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

3-[4′-(2-Hydroxy-ethoxymethyl)-biphenyl-4-ylmethyl]-1-oxa-3-aza-spiro[4.5]decan-2-one (85 mg, 0.215 mmol) was mixed with triethylamine (0.09 mL, 0.644 mmol) in DCM (3 mL). The mixture was cooled in ice-water bath. Methane sulfonylchloride (3.3 uL, 0.49 mmol) was added and the reaction mixture was allowed to warm to room temperature. The stirring was continued for further 2 hours. The reaction mixture was quenched with saturate NaHCO3 aqueous solution (3 mL). The aqueous phase was extracted with DCM (3×3 mL). The combined organic phase was dried over sodium sulfate and concentrated to give a brown oil which was mixed with dimethyl amine (4 mL, 6.44 mmol) in a screw cap vial and heated at 60˜70° C. for 3.5 hours. The reaction mixture was concentrated, redissolved in DCM (5 mL) and stirred with saturated NaHCO3 aqueous solution (3 mL). The aqueous phase was extracted with DCM (3×4 mL). The combined organic phases were dried over sodium sulfate and concentrated to give a pale brown oil, which was purified on silica gel eluting with DCM containing 1˜2.5% 2M ammonia in methanol to give the product as a white solid (74 mg, 82%). 1H NMR (300 MHz, CDCl3): δ (ppm) 7.56 (dd, 4H), 7.41 (d, 2H), 7.29 (d, 2H), 4.64 (s, 2H), 4.45 (s, 2H), 3.56 (t, 2H), 3.12 (s, 2H), 2.54 (t, 2H), 2.27 (s, 6H), 1.75 (m, 4H), 1.52 (m, 6H).

Workup

  1. customThe reaction mixture was quenched with saturate NaHCO3 aqueous solution (3 mL)
  2. extractionThe aqueous phase was extracted with DCM (3×3 mL)
  3. dry with materialThe combined organic phase was dried over sodium sulfate
  4. concentrationconcentrated
  5. customto give a brown oil which
  6. customcap vial
  7. temperatureheated at 60˜70° C. for 3.5 hours
  8. concentrationThe reaction mixture was concentrated
  9. dissolutionredissolved in DCM (5 mL)
  10. extractionThe aqueous phase was extracted with DCM (3×4 mL)
  11. dry with materialThe combined organic phases were dried over sodium sulfate
  12. concentrationconcentrated
  13. customto give a pale brown oil, which
  14. customwas purified on silica gel eluting with DCM containing 1˜2.5% 2M ammonia in methanol

Sources & evidence

ORD record
ord-1934d55b71ea4409ba9e411ffb65e87c
Source dataset
uspto-grants-2009_02
Patent number
US07485722B2

Reaction notes

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