Tetrahydrofuran → HCID 51003629, compound

HRID 1503347Notes

Reaction equation

HRID 1503347 reaction equation
Br[C:2]1[CH:31]=[CH:30][C:5]([O:6][CH2:7][CH2:8][CH2:9][N:10]2[CH2:15][CH2:14][CH:13]([C:16]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[OH:17])[CH2:12][CH2:11]2)=[CH:4][CH:3]=1.[N:32]1[CH:37]=[CH:36][C:35](B(O)O)=[CH:34][CH:33]=1.C1COCC1>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].O>[C:18]1([C:16]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)([CH:13]2[CH2:14][CH2:15][N:10]([CH2:9][CH2:8][CH2:7][O:6][C:5]3[CH:30]=[CH:31][C:2]([C:35]4[CH:36]=[CH:37][N:32]=[CH:33][CH:34]=4)=[CH:3][CH:4]=3)[CH2:11][CH2:12]2)[OH:17])[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 2734379(Pyridin-4-yl)boronic acidHCID 46926618HCID 46926618, compound

Product 1

HCID 51003629HCID 51003629, compoundYield 41.8%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

Bromide intermediate (1-(3-(4-bromophenoxy)propyl)piperidin-4-yl)diphenylmethanol (A1) (75 mg, 0.15 mmol), Pd(dppf)Cl2 (15 mg), CsCO3 (150 mg), and pyridin-4-ylboronic acid (30 mg) was placed under an argon atmosphere in a microwave vial. Degassed THF (3 mL) and 0.1 mL of water was added via syringe and the mixture heated for 30 min. at 90° C. in a Biotage microwave reactor. The reaction was partitioned between EtOAc (10 mL) and water (3 mL) and the organic phase isolated. The organic phase was subsequently washed with brine, dried over Na2SO4, and concentrated to dryness. Purification by RP-HPLC afforded the title compound (30 mg, 41%): LC-MS (>98%) m/z=479.1 [M+H].

Workup

  1. customThe reaction was partitioned between EtOAc (10 mL) and water (3 mL)
  2. customthe organic phase isolated
  3. washThe organic phase was subsequently washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated to dryness
  6. customPurification by RP-HPLC

Sources & evidence

ORD record
ord-67e90d5eb00744ca93c9cf7c9ba05f59
Source dataset
uspto-grants-2015_12
Patent number
US09212180B2

Reaction notes

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