Potassium Carbonate → 2'-Hydroxymethyl-3-methylamino-4-nitro-biphenyl-2-carbonitrile

HRID 2246896노트

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HRID 2246896 반응식
Cl[C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH3:11])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1.[OH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2N(C)C)CCCCC1>CC(N(C)C)=O.CCOC(C)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[OH:15][CH2:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[C:2]1[C:7]([C:8]#[N:9])=[C:6]([NH:10][CH3:11])[C:5]([N+:12]([O-:14])=[O:13])=[CH:4][CH:3]=1

참가 물질

8

반응물 4

HCID 11430Potassium CarbonateHCID 27342172-(Dicyclohexylphosphino)-2'-(dimethylamino)biphenylHCID 43742622-(Hydroxymethyl)phenylboronic AcidHCID 112180896-Chloro-2-(methylamino)-3-nitrobenzonitrile

생성물 1

HCID 592186742'-Hydroxymethyl-3-methylamino-4-nitro-biphenyl-2-carbonitrile수율 82%

시약·촉매·용매 3

HCID 9811564Bis(dibenzylideneacetone)palladium촉매HCID 8857Ethyl Acetate용매HCID 31374Dimethylacetamide용매

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온도
68 °C

실험 절차

6-Chloro-2-methylamino-3-nitro-benzonitrile (500 mg, 2.4 mmol), 2-hydroxymethyl-phenylboronic acid (466 mg, 3.1 mmol), and potassium carbonate (1.30 g, 6.1 mmol) were combined in DMA (10 mL) in a flask purged with nitrogen. Tris(dibenzylideneacetone)dipalladium(0) (108 mg, 0.12 mmol) and 2-dicyclohexylphosphino-2′-(N,N-dimethyl-amino)biphenyl (93 mg, 0.24 mmol) were added, and the reaction stirred at 68° C. under nitrogen for 16 h. The solution was diluted with EtOAc (50 mL), and washed with 1N HCl and brine. Organics were dried (MgSO4) and concentrated in vacuo. Purification by silica gel chromatography (2:1:1 hexanes/CHCl3/EtOAc) gave 550 mg (82%) of the title compound as an orange solid. 1H NMR (400 MHz, CDCl3): δ 8.49 (br s, 1H), 8.35 (d, 1H, J=8.8 Hz), 7.59 (d, 1H, J=7.6 Hz), 7.46 (td, 1H, J=7.6, 1.2 Hz), 7.40 (td, 1H, J=7.6, 1.2 Hz), 7.20 (dd, 1H, J=7.6, 1.2 Hz), 6.60 (d, 1H, J=8.8 Hz), 4.52 (qAB, 2H, J=31.6, 12.8 Hz), 3.46 (s, 3H). MS (ES) [m+H] calc'd for C15H13N3O3, 284; found 284.

후처리

  1. custompurged with nitrogen
  2. washwashed with 1N HCl and brine
  3. dry with materialOrganics were dried (MgSO4)
  4. concentrationconcentrated in vacuo
  5. customPurification by silica gel chromatography (2:1:1 hexanes/CHCl3/EtOAc)

출처 및 근거

ORD 기록
ord-5d7fcc08241f4d88bd462a222a786760
출처 데이터셋
uspto-grants-2010_03
특허 번호
US07687638B2

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