Methane, dichloromethoxy- → HCID 20728560, compound

HRID 898652Notes

Reaction equation

HRID 898652 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[O:12][CH2:11][CH2:10][CH2:9]2)=[O:5])[CH3:2].[CH3:16][O:17]C(Cl)Cl>C(Cl)Cl>[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]2[C:13](=[C:14]([CH:16]=[O:17])[CH:15]=1)[O:12][CH2:11][CH2:10][CH2:9]2)=[O:5])[CH3:2]

Participants

4

Reactant 2

HCID 21004Methane, dichloromethoxy-HCID 20728564HCID 20728564, compound2×

Product 1

HCID 20728560HCID 20728560, compound

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Compounds of the invention where the variable Y is an ethynyl-methyl (CH≡C—CH2—) group can, generally speaking, be synthesized in accordance with Reaction Scheme 12. The starting compound in accordance with this scheme is a 6-chromanoic acid ethyl ester derivative of Formula 3 which can be obtained as described above in connection with Reaction Scheme 1. The 6-chromanoic acid ethyl ester of Formula 3 is thereafter treated with α,α-dichloromethyl methyl ether in a suitable aprotic solvent such as methylene chloride to provide the 8-formyl-6-chromanoic acid ethyl ester derivative of Formula 12. The formyl compound of Formula 12 is reduced with sodium borohydride in methanol to give the corresponding hydroxymethyl compound of Formula 13. The hydroxymethyl compound of Formula 13 is then reacted with N-bromosuccinimide in the presence of triphenylphosphine in an aprotic solvent such as methylene chloride to give the 8-(bromomethyl)-6-chromanoic ester derivative of Formula 14. The 8-(bromomethyl)-6-chromanoic ester derivative of Formula 14 is reacted with trimethylsilyl acetylene in triethyl amine and dimethylformamide (DMF) under argon atmosphere in the presence of dichlorobis(triphenylphosphine)palladium(II) (Pd(PPh3)2Cl2). The trimethylsilyl group and the ethyl group of the ester moiety of the resulting 8-(trimethylsilylmethyl) 6-chromanoic acid ethyl ester are then removed by treatment with base (such as lithium hydroxide shown in the reaction scheme) to provide the 8-(ethynylmethyl)-6-chromanoic acid of Formula 15.

Workup

  1. custombe synthesized in accordance with Reaction Scheme 12
  2. customcan be obtained
  3. customas described above in connection with Reaction Scheme 1

Sources & evidence

ORD record
ord-51e0ac54080b424b9f395cf0f88c904b
Source dataset
uspto-grants-2008_04
Patent number
US07351737B2

Reaction notes

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