1,3-Dimethoxy-2-propanol → HCID 66897808, compound

HRID 1188927Notes

Reaction equation

HRID 1188927 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][N:17]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7]2.C(P(CCCC)CCCC)CCC.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.[CH3:57][O:58][CH2:59][CH:60](O)[CH2:61][O:62][CH3:63]>O1CCCC1>[CH3:57][O:58][CH2:59][CH:60]([CH2:61][O:62][CH3:63])[O:1][C:2]1[CH:3]=[C:4]([O:15][C:16]2[CH:21]=[CH:20][C:19]([S:22]([CH3:25])(=[O:24])=[O:23])=[CH:18][N:17]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH3:14])=[O:12])=[CH:7]2

Participants

6

Reactant 4

HCID 121901,3-Dimethoxy-2-propanol3×HCID 13831Tributylphosphine3×HCID 730421,1'-(Azodicarbonyl)dipiperidine3×HCID 67118474HCID 67118474, compound

Product 1

HCID 66897808HCID 66897808, compoundYield 97%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of methyl 7-hydroxy-5-{[5-(methylsulfonyl)pyridin-2-yl]oxy}-1H-indole-2-carboxylate (2.75 g), tributylphosphine (3.7 mL), 1,1′-(azodicarbonyl)dipiperidine (3.8 g), 1,3-dimethoxypropan-2-ol (1.8 g) and tetrahydrofuran (50 mL) was stirred at 50° C. for 8 h. Tributylphosphine (1.9 mL), 1,1′-(azodicarbonyl)dipiperidine (1.9 g) and 1,3-dimethoxypropan-2-ol (0.9 g) were added to the mixture again, and the mixture was stirred at 50° C. for 8 h. Furthermore, tributylphosphine (3.7 mL), 1,1′-(azodicarbonyl)dipiperidine (3.8 g) and 1,3-dimethoxypropan-2-ol (1.8 g) were added to the mixture. After stirring at 50° C. for 24 h, the mixture was cooled to 0° C. and a precipitate was removed by filtration. The filtrate was concentrated and the residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90 to 80/20, volume ratio) twice, followed by basic silica gel column chromatography (ethyl acetate/hexane 20/80 to 85/15) to give the crude title compound (3.42 g) as a yellow oil. MS 465 (MH+).

Workup

  1. stirringthe mixture was stirred at 50° C. for 8 h
  2. stirringAfter stirring at 50° C. for 24 h
  3. temperaturethe mixture was cooled to 0° C.
  4. customa precipitate was removed by filtration
  5. concentrationThe filtrate was concentrated
  6. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane=10/90 to 80/20, volume ratio) twice

Sources & evidence

ORD record
ord-cbdb7971e965406c9fcfc4b9c97a9ef4
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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