Tributylphosphine → Ethyl 5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxylate

HRID 1042097Notes

Reaction equation

HRID 1042097 reaction equation
[OH:1][C:2]1[CH:3]=[C:4]([O:16][C:17]2[CH:22]=[CH:21][C:20]([S:23]([CH3:26])(=[O:25])=[O:24])=[CH:19][CH:18]=2)[CH:5]=[C:6]2[C:10]=1[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]2.[O:27]1[CH2:32][CH2:31][CH:30](O)[CH2:29][CH2:28]1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.C(P(CCCC)CCCC)CCC>O1CCCC1>[CH3:26][S:23]([C:20]1[CH:21]=[CH:22][C:17]([O:16][C:4]2[CH:5]=[C:6]3[C:10](=[C:2]([O:1][CH:30]4[CH2:31][CH2:32][O:27][CH2:28][CH2:29]4)[CH:3]=2)[NH:9][C:8]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:7]3)=[CH:18][CH:19]=1)(=[O:25])=[O:24]

Participants

6

Reactant 4

HCID 13831Tributylphosphine2×HCID 730421,1'-(Azodicarbonyl)dipiperidine2×HCID 74956Tetrahydro-4H-pyran-4-ol2×HCID 66726144Ethyl 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate

Product 1

HCID 66726153Ethyl 5-[4-(methylsulfonyl)phenoxy]-7-(tetrahydro-2H-pyran-4-yloxy)-1H-indole-2-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of ethyl 7-hydroxy-5-[4-(methylsulfonyl)phenoxy]-1H-indole-2-carboxylate (2.0 g), tetrahydro-2H-pyran-4-ol (2.02 mL), 1,1′-(azodicarbonyl)dipiperidine (5.3 g), tributylphosphine (5.3 mL), and tetrahydrofuran(60 mL) was stirred at 70° C. for 6 hr. To the reaction solution were added tetrahydro-2H-pyran-4-ol (1.02 mL), 1,1′-(azodicarbonyl)dipiperidine (2.5 g) and tributylphosphine (2.5 mL) and the mixture was stirred at 70° C. for 14 hr. The reaction solution was concentrated under reduced pressure to a half volume and the precipitated solid was filtered off. The filtrate was concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (volume ratio, ethyl acetate:hexane=5:95 to 50:50), and then basic silica gel column chromatography (volume ratio, methanol:ethyl acetate:hexane=0:2:98 to 20:80:0) to give the title compound (5.33 g) as a yellow oily crude product.

Workup

  1. stirringthe mixture was stirred at 70° C. for 14 hr
  2. concentrationThe reaction solution was concentrated under reduced pressure to a half volume
  3. filtrationthe precipitated solid was filtered off
  4. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-0527501416be42938ac0382e6fab469f
Source dataset
uspto-grants-2013_10
Patent number
US08557805B2

Reaction notes

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