Oxalyl chloride → 4-(cyanoMethylcarbaMoyl)phenylboronic acid

HRID 591128Notes

Reaction equation

HRID 591128 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([B:10]([OH:12])[OH:11])=[CH:6][CH:5]=1)([OH:3])=O.C(Cl)(=O)C(Cl)=O.Cl.[NH2:20][CH2:21][C:22]#[N:23].CCN(C(C)C)C(C)C>CN(C=O)C.ClCCl>[C:21]([CH2:22][NH:23][C:1]([C:4]1[CH:9]=[CH:8][C:7]([B:10]([OH:12])[OH:11])=[CH:6][CH:5]=1)=[O:3])#[N:20]

Participants

7

Reactant 4

HCID 65578Oxalyl chlorideHCID 81531DiisopropylethylamineHCID 3121834-Carboxyphenylboronic AcidHCID 11491918Aminoacetonitrile hydrochloride

Product 1

HCID 866438164-(cyanoMethylcarbaMoyl)phenylboronic acidYield 87.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolvent2×HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 4-carboxyphenylboronic acid (5.0 g, 30 mmol) in DMF (5 mL) and dichloromethane (200 mL) at 0° C. was added oxalylchloride (5.9 mL, 66 mmol) dropwise. When gas evolution slowed, the ice bath was removed and the reaction allowed to warm to room temperature over 30 min. The reaction was then heated at 40° C. for three hours by which time all solids had dissolved. The dichloromethane was removed by distillation and the DMF solution cooled to 0° C. A solution of aminoacetonitrile hydrochloride (3.05 g, 33 mmol) in DMF (80 mL) and DIPEA (13 mL, 75 mmol) was then added dropwise. After the addition was complete the ice bath was removed and the solution allowed to stir at room temperature for 16 h. Most of the DMF was then removed in vacuo and the reaction was partitioned between ethyl acetate and 2 M aqueous hydrochloric acid. The aqueous layer was extracted twice further with ethyl acetate and the combined organic fractions dried (Na2SO4) filtered and concentrated under reduced pressure to afford 4-(cyanomethylcarbamoyl)phenylboronic acid as a waxy pale yellow solid (5.34 g, 87%). 1H NMR (300 MHz, d6-DMSO): 9.18 (br. t, J=5.1 Hz, 1H), 7.8-7.9 (m, 4H), 4.31 (d, J=5.4 Hz, 2H); LC-ESI-MS (method B): rt 0.9 min.; m/z 203.3 [M−H]−.

Workup

  1. customthe ice bath was removed
  2. temperatureThe reaction was then heated at 40° C. for three hours by which time all solids
  3. dissolutionhad dissolved
  4. customThe dichloromethane was removed by distillation
  5. temperaturethe DMF solution cooled to 0° C
  6. additionAfter the addition
  7. customwas removed
  8. customMost of the DMF was then removed in vacuo
  9. customthe reaction was partitioned between ethyl acetate and 2 M aqueous hydrochloric acid
  10. extractionThe aqueous layer was extracted twice further with ethyl acetate
  11. dry with materialthe combined organic fractions dried (Na2SO4)
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-920672b22b3d48c3a6e9e2d5a0fa3221
Source dataset
uspto-grants-2016_01
Patent number
US09238628B2

Reaction notes

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