Methanol → HCID 10382175, compound

HRID 1725870Notes

Reaction equation

HRID 1725870 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])=[C:6]([CH:11]=1)[C:7]([O:9]C)=[O:8].[Br-].[CH2:23]([Zn+])[CH:24]([CH3:26])[CH3:25].[OH-].[Na+].CO>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Cu]I.C1COCC1>[CH2:23]([C:2]1[CH:3]=[CH:4][C:5]([NH:12][S:13]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)(=[O:15])=[O:14])=[C:6]([CH:11]=1)[C:7]([OH:9])=[O:8])[CH:24]([CH3:26])[CH3:25]

Participants

8

Reactant 4

HCID 887MethanolHCID 14798Sodium HydroxideHCID 8189263HCID 8189263, compoundHCID 178448254HCID 178448254, compound

Product 1

HCID 10382175HCID 10382175, compound

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
160 °C

Procedure

A mixture of Example 4A (0.09 g, 0.24 mmol), Pd(dppf)Cl2 (5 mol %), and CuI (6 mol %) was sealed using a crimper and treated with a solution of isobutylzinc bromide (0.5M in THF, 0.96 mL, 0.48 mmol). The reaction was heated in a single-mode microwave cavity in the Smith synthesizer at 160° C. for 600 seconds and filtered through a 1 micron PTFE syringe filter. The filtrate was concentrated, dissolved in 1:1 CH3OH:DMSO (1.5 mL), and purified using a C18 reverse-phase HPLC with acetonitrile/water/1% TFA. The purified ester was saponified by treatment with 10 equivalents of 2N NaOH in 1:1 CH3OH:THF at 70° C. for 48 hours. The mixture was extracted with ethyl acetate and the extract was concentrated to provide the desired product. MS (ESI(+)) m/e 334 (M+H)+, 351 (M+NH4)+, 356 (M+Na)+; 1H NMR (300 MHz, DMSO-d6) δ 10.90 (s, 1H), 7.80 (m, 2H), 7.40 (m, 3H), 7.10 (s, 1H), 6.80 (m, 1H), 6.50 (m, 1H), 2.20 (d, 2H), 1.70 (m, 1H), 0.80 (d, 6H).

Workup

  1. filtrationfiltered through a 1 micron PTFE syringe
  2. filtrationfilter
  3. concentrationThe filtrate was concentrated
  4. dissolutiondissolved in 1:1 CH3OH
  5. customDMSO (1.5 mL), and purified
  6. extractionThe mixture was extracted with ethyl acetate
  7. concentrationthe extract was concentrated

Sources & evidence

ORD record
ord-9f7d4eef64b6441c9cb92ea03bb352d2
Source dataset
uspto-grants-2009_02
Patent number
US07491718B2

Reaction notes

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