Sodium Carbonate → 5-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile

HRID 2120727

반응식

HRID 2120727 반응식
Br[C:2]1[CH:3]=[CH:4][C:5]2[NH:10][CH:9]([CH3:11])[O:8][C:7]([CH3:13])([CH3:12])[C:6]=2[CH:14]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C([O-])(=O)C.[K+].Br[C:39]1[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=1.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.[Cl-].[Na+].O.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].C(OCC)(=O)C>[CH3:11][CH:9]1[O:8][C:7]([CH3:13])([CH3:12])[C:6]2[CH:14]=[C:2]([C:39]3[S:43][C:42]([C:44]#[N:45])=[CH:41][CH:40]=3)[CH:3]=[CH:4][C:5]=2[NH:10]1

참가 물질

10

반응물 5

HCID 10340Sodium CarbonateHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 35950595-Bromothiophene-2-carbonitrileHCID 234355746-Bromo-2,4,4-trimethyl-2,4-dihydro-1H-benzo[D][1,3]oxazine

생성물 1

HCID 120431855-(2,4,4-Trimethyl-1,4-dihydro-2H-3,1-benzoxazin-6-yl)thiophene-2-carbonitrile수율 25.1%

시약·촉매·용매 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)촉매2회HCID 6228Dimethylformamide용매HCID 8857Ethyl Acetate용매HCID 57417360Sodium chloride; water용매

반응 조건

온도
85 °C

실험 절차

A mixture of 6-bromo-2,4,4-trimethyl-1,4-dihydro-2H-3,1-benzoxazine (3.6 g, 14 mmol), bis(pinacolato)diboron (5 g, 19.7 mmol), potassium acetate (4 g, 41 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol) in DMF (80 mL) was subject to a positive nitrogen flow to remove oxygen and then heated at 85° C. under a blanket of nitrogen for 18 hours. The mixture was allowed to cool to ambient temperature, treated with 5-bromo-2-thiophenecarbonitrile (4 g, 21 mmol), [1,1′-bis(diphenylphosphino)ferrocene]palladium (II) chloride (1:1 complex with methylene chloride, 0.4 g, 0.5 mmol), and aqueous sodium carbonate solution (2M, 35 mL, 70 mmol), and then heated at 85° C. under nitrogen for 3 hours. The reaction mixture was allowed to cool to ambient temperature, brine (100 mL) and ethyl acetate (150 mL) were added. The organic layer was separated and aqueous layer was extracted with ethyl acetate (3×50 mL). The combined organic layers were dried (MgSO4) and concentrated. The residue was purified by a flash silica gel column chromatography (THF:hexane/1:4) to afford the title compound as an off-white solid (1 g, 25%): mp 172-173° C.; 1H-NMR (DMSO-d6) δ 7.88 (d, 1H, J=4.0 Hz), 7.47 (d, 1H, J=4.0 Hz), 7.43 (d, 1H, J=2.0 Hz), 7.32 (dd, 1H, J=8.36, 2.4 Hz), 6.77 (s, 1H), 6.60 (d, 1H, J=8.4 Hz), 4.83 (m, 1H), 1.51 (s, 3H), 1.48 (s, 3H), 1.28 (d, 3H, J 5.6 Hz); MS (ESI) m/z 283 [M−H]−.

후처리

  1. customto remove oxygen
  2. temperatureto cool to ambient temperature
  3. temperatureheated at 85° C. under nitrogen for 3 hours
  4. temperatureto cool to ambient temperature
  5. customThe organic layer was separated
  6. extractionaqueous layer was extracted with ethyl acetate (3×50 mL)
  7. dry with materialThe combined organic layers were dried (MgSO4)
  8. concentrationconcentrated
  9. customThe residue was purified by a flash silica gel column chromatography (THF:hexane/1:4)

출처 및 근거

ORD 기록
ord-7f151905f03244998f90c73af20be4e8
출처 데이터셋
uspto-grants-2004_02
특허 번호
US06693103B2

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