1-Methoxy-2-propanol → HCID 66897975, compound

HRID 1188952Notes

Reaction equation

HRID 1188952 reaction equation
[CH2:1]([S:8][CH:9]([CH:35]([O:38][CH3:39])[O:36][CH3:37])[CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([O:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:32])=[O:31])=[CH:26][CH:25]=1)=[CH:18][C:17]=2[OH:34])=[O:13])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(P(CCCC)CCCC)CCC.[CH3:53][O:54][CH2:55][CH:56](O)[CH3:57].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>O1CCCC1>[CH2:1]([S:8][CH:9]([CH:35]([O:38][CH3:39])[O:36][CH3:37])[CH2:10][NH:11][C:12]([C:14]1[NH:15][C:16]2[C:21]([CH:22]=1)=[CH:20][C:19]([O:23][C:24]1[CH:29]=[CH:28][C:27]([S:30]([CH3:33])(=[O:31])=[O:32])=[CH:26][CH:25]=1)=[CH:18][C:17]=2[O:34][CH:56]([CH3:57])[CH2:55][O:54][CH3:53])=[O:13])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 79001-Methoxy-2-propanol2×HCID 13831Tributylphosphine2×HCID 730421,1'-(Azodicarbonyl)dipiperidine2×HCID 58236936HCID 58236936, compound

Product 1

HCID 66897975HCID 66897975, compoundYield 82%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
50 °C

Procedure

To a stirred solution of N-[2-(benzylsulfanyl)-3,3-dimethoxypropyl]-7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxamide (1.73 g), tributylphosphine (1.4 mL) and 1-methoxypropan-2-ol (0.59 mL) in tetrahydrofuran (50 mL) was added 1,1′-(azodicarbonyl)dipiperidine (1.53 g) at room temperature under argon atmosphere. The whole mixture was stirred at 50° C. for 4 h, and tributylphosphine (1.4 mL), and 1-methoxypropan-2-ol (0.59 mL) and 1,1′-(azodicarbonyl)dipiperidine (1.53 g) were added thereto. After stirred at 50° C. for 3 h, the reaction mixture was concentrated in vacuo. The residue was diluted with diethyl ether and the insoluble materials were removed by filtration and washed with diethyl ether. The combined filtrate and washings were concentrated in vacuo and the residue was purified by silica gel chromatography (ethyl acetate:hexane=35:65 to 60:40) to give a light yellow oil. The oil was partitioned between ethyl acetate and water. The organic layer was washed with successively water and brine, dried (MgSO4), filtered, and concentrated to give a yellow oil, which was purified by silica gel chromatography (ethyl acetate:hexane=35:65 to 70:30, volume ratio) to give the title compound (1.6 g, 82%) as a pale yellow oil. MS 641 (MH+).

Workup

  1. stirringAfter stirred at 50° C. for 3 h
  2. concentrationthe reaction mixture was concentrated in vacuo
  3. additionThe residue was diluted with diethyl ether
  4. customthe insoluble materials were removed by filtration
  5. washwashed with diethyl ether
  6. concentrationThe combined filtrate and washings were concentrated in vacuo
  7. customthe residue was purified by silica gel chromatography (ethyl acetate:hexane=35:65 to 60:40)
  8. customto give a light yellow oil
  9. customThe oil was partitioned between ethyl acetate and water
  10. washThe organic layer was washed with successively water and brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customto give a yellow oil, which
  15. customwas purified by silica gel chromatography (ethyl acetate:hexane=35:65 to 70:30, volume ratio)

Sources & evidence

ORD record
ord-f7f3737396e24ab3affe8ff865c1dad0
Source dataset
uspto-grants-2014_03
Patent number
US08673942B2

Reaction notes

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