Formic Acid → HCID 118131333, compound

HRID 634427Notes

Reaction equation

HRID 634427 reaction equation
[C:1]1(B(O)O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.Cl[C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:14][O:13][C:12]=1[CH:21]=[O:22].C(#N)C.C(O)=O>C1COCC1.O.CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C.[Pd]>[C:1]1([C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][O:13][C:12]=2[CH:21]=[O:22])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 4

HCID 284Formic AcidHCID 6342AcetonitrileHCID 66827Phenylboronic AcidHCID 118131408HCID 118131408, compound

Product 1

HCID 118131333HCID 118131333, compoundYield 94.4%

Reagents, catalysts & solvents 3

HCID 86677350Pd XPhosCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Procedure

X-phos Pd G2 (116 mg, 0,147 mmol) and phenylboronic acid (538 mg, 4.41 mmol) were sealed in a closed vessel equipped with a magnetic bar and oxygen removed by Ar/vacuum cycle. A degassed solution of 4-chloro-1H-isochromene-3-carbaldehyde (Intermediate G20.1, 716 mg, 3.68 mmol) in THF (8 ml) was added followed by a degassed solution of K3PO4H2O (1,795 ml, 7.36 mmol) in water (8 ml) and the resulting mixture stirred at rt overnight. The reaction mixture was partitioned between 1M HCl (15 ml) and the same amount of AcOEt. The organic layer was anhydrified over Na2SO4, evaporated in vacuo and purified via reverse phase chromatography with a Biotage C18 SNAP 120 g column (Phase A, water 95%, ACN 5%, formic acid 0.1%); Phase B ACN 95%, water 5%, formic acid 0.1%) to give the title compound (821 mg, 94% yield).

Workup

  1. customequipped with a magnetic bar
  2. customoxygen removed by Ar/vacuum cycle
  3. customThe reaction mixture was partitioned between 1M HCl (15 ml)
  4. customevaporated in vacuo
  5. custompurified via reverse phase chromatography with a Biotage C18 SNAP 120 g column (Phase A, water 95%, ACN 5%, formic acid 0.1%)

Sources & evidence

ORD record
ord-d6dbb45c79c54aacbf5f715b02b14149
Source dataset
uspto-grants-2016_04
Patent number
US09321776B2

Reaction notes

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