Diisopropylethylamine → 4-(4'-Chloro-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acid

HRID 2266795Notes

Reaction equation

HRID 2266795 reaction equation
C1C=CC(C(Cl)([C:14]2[C:19]([Cl:20])=[CH:18][CH:17]=[CH:16][CH:15]=2)C2C=CC=CC=2)=CC=1.I[C:23]1[CH:39]=[CH:38][C:26]([O:27][CH2:28][C:29]2[CH:30]=[C:31]([C:35]([OH:37])=[O:36])[O:32][C:33]=2[CH3:34])=[CH:25][CH:24]=1.C(N(C(C)C)CC)(C)C>ClCCl>[Cl:20][C:19]1[CH:14]=[CH:15][C:16]([C:23]2[CH:39]=[CH:38][C:26]([O:27][CH2:28][C:29]3[CH:30]=[C:31]([C:35]([OH:37])=[O:36])[O:32][C:33]=3[CH3:34])=[CH:25][CH:24]=2)=[CH:17][CH:18]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 945242-Chlorotrityl chlorideHCID 184446544-(4-Iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid

Product 1

HCID 184445594-(4'-Chloro-biphenyl-4-yloxymethyl)-5-methyl-furan-2-carboxylic acidYield 3.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

2-Chlorotrityl chloride resin (2.55 g of nominal loading 1.3 mmol/g) was swelled with dichloromethane (20 mL). After draining, a solution of 4-(4-iodo-phenoxymethyl)-5-methyl-furan-2-carboxylic acid (26) (1.18 g) and diisopropylethylamine (2.3 mL) in dichloromethane (30 mL) was added and the mixture was shaken at room temperature for 72 hours. The resin was drained, washed sequentially with dichloromethane/triethylamine/methanol (20:1:3 by volume) (3×30 mL), dichloromethane (6×30 mL), N,N-dimethylformamide (2×25 mL), dichloromethane (6×25 mL), and diethyl ether (2×25 mL) and dried at 40° C. in vacuo, (ii) A stirred mixture of the resin from (i) (0.38 g), 4-chlorophenylboronic acid (0.30 g), [1,1′-bis-(diphenylphosphino)-ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (30 mg), potassium acetate (0.20 g) in N,N-dimethylformamide (15 mL) was heated at 40° C. for 48 hours. The resin was drained, then washed sequentially with tetrahydrofuran/water (1:1 by volume), tetrahydrofuran, N,N-dimethylformamide, dichloromethane, diethyl ether and then dried at 45° C. in vacuo. The resin was treated with dichloromethane/trifluoroacetic acid (19:1 by volume) (20 mL) for 20 mins and the solution drained from the resin. This procedure was repeated. The combined solutions were concentrated in vacuo and the residue purified by HPLC to afford compound 27 as a white solid (43 mg). LC/MS System D: Rt=8.83 mins, m/z (ES−)=341 (M− for C19H15ClO4).

Workup

  1. washwashed sequentially with dichloromethane/triethylamine/methanol (20:1:3 by volume) (3×30 mL), dichloromethane (6×30 mL), N,N-dimethylformamide (2×25 mL), dichloromethane (6×25 mL), and diethyl ether (2×25 mL)
  2. dry with materialdried at 40° C. in vacuo, (ii)
  3. additionA stirred mixture of the resin from (i) (0.38 g), 4-chlorophenylboronic acid (0.30 g), [1,1′-bis-(diphenylphosphino)-ferrocene]-dichloropalladium(II) complex with dichloromethane (1:1) (30 mg), potassium acetate (0.20 g) in N,N-dimethylformamide (15 mL)
  4. temperaturewas heated at 40° C. for 48 hours
  5. washwashed sequentially with tetrahydrofuran/water (1:1 by volume), tetrahydrofuran, N,N-dimethylformamide, dichloromethane, diethyl ether
  6. customdried at 45° C. in vacuo
  7. additionThe resin was treated with dichloromethane/trifluoroacetic acid (19:1 by volume) (20 mL) for 20 mins
  8. concentrationThe combined solutions were concentrated in vacuo
  9. customthe residue purified by HPLC

Sources & evidence

ORD record
ord-0893c2e08b3b4dddb1cf68c452717102
Source dataset
uspto-grants-2010_12
Patent number
US07858644B2

Reaction notes

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