Tetrahydrofuran → N-(2(R)-hydroxy-1(S)-indanyl)-trans-3-(4-pyridyl) acrylamide

HRID 2396319Notes

Reaction equation

HRID 2396319 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](/[CH:7]=[CH:8]/[C:9]([OH:11])=O)=[CH:3][CH:2]=1.C([N:14]([CH2:17][CH3:18])CC)C.[CH3:19][C:20](C)(C)[C:21](Cl)=[O:22].[CH2:26]1[CH2:30]O[CH2:28][CH2:27]1>>[OH:22][C@@H:21]1[CH2:20][C:19]2[C:18](=[CH:30][CH:26]=[CH:27][CH:28]=2)[C@@H:17]1[NH:14][C:9](=[O:11])/[CH:8]=[CH:7]/[C:4]1[CH:3]=[CH:2][N:1]=[CH:6][CH:5]=1

Participants

5

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 8471TriethylamineHCID 62493Pivaloyl chlorideHCID 7367823-(4-Pyridine)acrylic acid

Product 1

HCID 15389521N-(2(R)-hydroxy-1(S)-indanyl)-trans-3-(4-pyridyl) acrylamide

Conditions

Temperature
0 °C

Procedure

To a suspension of trans-3-(4-pyridyl)acrylic acid (10.0 g, 0.067 mol) in 500 mL of THF was added triethylamine (10.29 mL, 0.0738 mol) and the solution was cooled to 0° C. Trimethylacetyl chloride (8.68 mL, 0.0704 mol) was added and the reaction stirred for 0.5 h. 2(R)-hydroxy-1(S)-indane (10.0 g, 0.067 mol) dissolved in 260 mL of THF was added via cannula. After 2 h the reaction was warmed to RT and stirred an additional 15 h. The solvent was removed in vacuo and the resulting solid was triturated with cold ethyl acetate (150 mL) and filtered. This was dried overnight under vacuum (0.5 mm of Hg) to provide 18.5 g of a white solid; mp 205°-207° C.

Workup

  1. additionwas added via cannula
  2. temperatureAfter 2 h the reaction was warmed to RT
  3. stirringstirred an additional 15 h
  4. customThe solvent was removed in vacuo
  5. customthe resulting solid was triturated with cold ethyl acetate (150 mL)
  6. filtrationfiltered
  7. customThis was dried overnight under vacuum (0.5 mm of Hg)

Sources & evidence

ORD record
ord-ff5c6868d84742dcb05076f2cfb3fff3
Source dataset
uspto-grants-1996_02
Patent number
US05491238

Reaction notes

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