Oxalyl chloride → 4-(Cyanomethyl-carbamoyl)phenyl-boronic acid

HRID 589572노트

반응식

HRID 589572 반응식
[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]

참가 물질

7

반응물 4

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

생성물 1

HCID 866438164-(Cyanomethyl-carbamoyl)phenyl-boronic acid수율 87.3%

시약·촉매·용매 2

HCID 6228Dimethylformamide용매2회HCID 6344Dichloromethane용매

실험 절차

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=5.1Hz, 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]−.

후처리

  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

출처 및 근거

ORD 기록
ord-8c819ef967444ab982eb2f04ce6646dd
출처 데이터셋
uspto-grants-2016_01
특허 번호
US09233934B2

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