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Potassium Carbonate → tert-butyl 6-(6-(methoxycarbonyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate

HRID 1641112
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HRID 1641112 반응식
CC1(C)C(C)(C)OB([C:9]2[CH:25]=[CH:24][C:12]3[O:13][CH2:14][CH2:15][N:16]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[C:11]=3[CH:10]=2)O1.Br[C:28]1[N:33]=[C:32]([C:34]([O:36][CH3:37])=[O:35])[C:31]([O:38][CH2:39][CH2:40][CH2:41][O:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)=[CH:30][CH:29]=1.C([O-])([O-])=O.[K+].[K+].O1CCO[CH2:57][CH2:56]1>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.CCOC(C)=O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:37][O:36][C:34]([C:32]1[N:33]=[C:28]([C:9]2[CH:25]=[CH:24][C:12]3[O:13][CH2:14][CH2:15][N:16]([C:17]([O:19][C:20]([CH3:21])([CH3:22])[CH3:23])=[O:18])[C:11]=3[CH:10]=2)[CH:29]=[CH:30][C:31]=1[O:38][CH2:39][CH2:40][CH2:41][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:35].[CH3:37][O:36][C:34]([C:32]1[N:33]=[C:28]([C:9]2[CH:25]=[CH:24][C:12]3[O:13][CH2:14][CH2:15][N:16]([C:17]([O:19][CH2:20][CH2:23][CH2:56][CH3:57])=[O:18])[C:11]=3[CH:10]=2)[CH:29]=[CH:30][C:31]=1[O:38][CH2:39][CH2:40][CH2:41][O:42][C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)=[O:35]
참가 물질반응 조건실험 절차후처리출처 및 근거반응 노트

참가 물질

9

반응물 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 59418692tert-Butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-4H-1,4-benzoxazine-4-carboxylateHCID 59418768HCID 59418768, 화합물

생성물 2

HCID 59418702tert-butyl 6-(6-(methoxycarbonyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate
HCID 86643667
HCID 86643667, 화합물

시약·촉매·용매 3

HCID 74236Tetrabutylammonium Bromide촉매HCID 178418476HCID 178418476, 화합물촉매HCID 8857Ethyl Acetate용매

반응 조건

온도
90 °C

실험 절차

A mixture of tert-butyl 6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (53B) (72 mg, 0.20 mmol), methyl 6-bromo-3-(3-phenoxypropoxy)picolinate (26C) (72 mg, 0.20 mmol), K2CO3 (30 mg, 0.22 mmol in 0.5 mL of water), tetrabutyl ammonium bromide (64 mg, 0.20 mmol) and dichlorobis(triphenylphosphine)palladium (II) (10 mg, catalytic amount) in 1,4-dioxane (5 mL) was heated to 90° C. for 6 hours. The reaction mixture was cooled to rt, diluted with EtOAc, filtered through Celite, and concentrated under reduced pressure. The crude material was purified by column chromatography on silica gel eluting with 20% EtOAc in hexanes to provide the desired product tent-butyl 6-(6-(methoxycarbonyl)-5-(3-phenoxypropoxy)pyridin-2-yl)-2H-benzo[b][1,4]oxazine-4(3H)-carboxylate (53C). 1H NMR (300 MHz, CDCl3): 8.49 (1H, s), 7.74 (1H, d), 7.60 (1H, d), 7.38 (1H, d), 7.24 (2H, m), 6.90 (4H, m), 4.31 (2H, t), 4.18 (2H, t), 4.25 (2H, t), 3.95 (3H, s), 3.85 (2H, t), 2.3 (2H, m), 1.58 (9H, s). LCMS (APCI): m/z 521.1 (M+H).

후처리

  1. temperatureThe reaction mixture was cooled to rt
  2. filtrationfiltered through Celite
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by column chromatography on silica gel eluting with 20% EtOAc in hexanes

출처 및 근거

ORD 기록
ord-7a2b285ee4854eeeafad3810644b9f34
출처 데이터셋
uspto-grants-2012_02
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08114893B2

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