Triethylamine → HCID 24984414, compound

HRID 1724078Notes

Reaction equation

HRID 1724078 reaction equation
[CH2:1]([N:4]1[CH2:8][C:7]2([CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[O:6][C:5]1=[O:14])[C:2]#[CH:3].I[C:16]1[CH:28]=[CH:27][C:19]([CH2:20][N:21]2[CH2:26][CH2:25][O:24][CH2:23][CH2:22]2)=[CH:18][CH:17]=1.C(N(CC)CC)C>C(#N)C.ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu](I)I>[N:21]1([CH2:20][C:19]2[CH:18]=[CH:17][C:16]([C:3]#[C:2][CH2:1][N:4]3[CH2:8][C:7]4([CH2:9][CH2:10][CH2:11][CH2:12][CH2:13]4)[O:6][C:5]3=[O:14])=[CH:28][CH:27]=2)[CH2:22][CH2:23][O:24][CH2:25][CH2:26]1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 27955004-(4-Iodobenzyl)morpholineHCID 57559825HCID 57559825, compound

Product 1

HCID 24984414HCID 24984414, compoundYield 41.1%

Reagents, catalysts & solvents 4

HCID 83717Copper iodideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

3-Prop-2-ynyl-1-oxa-3-aza-spiro[4.5]decan-2-one(55 mg, 0.284 mmol), 4-(4-iodo-benzyl)-morpholine(95 mg, 0.313 mmol), tetrakis(triphenylphosphine)palladium (17 mg, 0.0142 mmol), copper iodide (6 mg, 0.0284 mmol) and triethylamine (0.12 mL, 0.853 mmol) were mixed in acetonitrile (1 mL) under argon. The reaction mixture was stirred at room temperature for 1 hour and then diluted with dichloromethane (6 mL). The mixture was washed with water (4 mL), washed with brine (4 mL), dried over sodium sulfate and concentrated. The residue was purified on silica gel eluting with 10 to 25% ethyl acetate in hexanes. The isolated product was treated with 2M hydrochloric acid in diethyl ether to make the hydrochloric acid salt. The salt was then dissolved in water, washed with hexanes and the aqueous phase then made alkaline using aqueous saturated sodium bicarbonate. The aqueous mixture was then extracted with dichloromethane and the organic phase dried over sodium sulfate and concentrated to give the product as an off-white solid (43 mg, 41%). 1H NMR (300 MHz, CDCl3): δ 7.38 (d, 2H), 7.29 (d, 2H), 4.31 (s, 2H), 3.71 (t, 4H), 3.49 (s, 2H), 3.4 (s, 2H), 2.43 (t, 4H), 1.83 (m, 4H), 1.54 (m, 6H).

Workup

  1. washThe mixture was washed with water (4 mL)
  2. washwashed with brine (4 mL)
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated
  5. customThe residue was purified on silica gel eluting with 10 to 25% ethyl acetate in hexanes
  6. additionThe isolated product was treated with 2M hydrochloric acid in diethyl ether
  7. dissolutionThe salt was then dissolved in water
  8. washwashed with hexanes
  9. extractionThe aqueous mixture was then extracted with dichloromethane
  10. dry with materialthe organic phase dried over sodium sulfate
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-14d03cd12a8546e4874b169bc358e158
Source dataset
uspto-grants-2009_02
Patent number
US07485722B2

Reaction notes

Loading…