Cesium carbonate → Tert-butyl (4-((2-chloropyridin-4-yl)methoxy)naphthalen-1-yl)carbamate

HRID 63359

반응식

HRID 63359 반응식
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8]Cl)[CH:5]=[CH:4][N:3]=1.[OH:10][C:11]1[C:20]2[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=2)[C:14]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C(#N)C.CO.C(Cl)Cl.O>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][O:10][C:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[C:14]([NH:21][C:22](=[O:28])[O:23][C:24]([CH3:26])([CH3:25])[CH3:27])=[CH:13][CH:12]=2)[CH:5]=[CH:4][N:3]=1

참가 물질

8

반응물 3

HCID 10796Cesium carbonateHCID 10923237tert-Butyl (4-hydroxynaphthalen-1-yl)carbamateHCID 111265732-Chloro-4-(chloromethyl)pyridine

생성물 1

HCID 118317288Tert-butyl (4-((2-chloropyridin-4-yl)methoxy)naphthalen-1-yl)carbamate수율 72.6%

시약·촉매·용매 4

HCID 887Methanol용매HCID 962Water용매HCID 6342Acetonitrile용매HCID 6344Dichloromethane용매

반응 조건

온도
55 °C

실험 절차

To a mixture of 2-chloro-4-(chloromethyl)pyridine (30 g, 185 mmol) and tert-butyl (4-hydroxynaphthalen-1-yl)carbamate (40.0 g, 154 mmol) in acetonitrile (200 mL) was added caesium carbonate (75 g, 231 mmol) and the resulting mixture was heated to 55° C. After 16 h the reaction mixture was diluted with 30% MeOH in DCM (600 mL) and water (400 mL). The layers were separated and the aqueous layer was extracted with a further amount of 30% MeOH in DCM (2×600 mL) and the organics were concentrated in vacuo to afford the crude product. The crude product was triturated with MeOH (200 mL), sonicated for c.a. 5 min and slurried for 1 day. The resulting solid was collected by filtration and washed with MeOH (2×10 mL) to yield the subtitle compound tert-butyl (4-((2-chloropyridin-4-yl)methoxy)naphthalen-1-yl)carbamate as a yellow solid (43 g, 70%); Rt 2.60 min (Method 1); m/z 383 (M−H)− (ES−); 1H NMR δ:1.47 (9H, s), 5.41 (2H, s), 6.98 (1H, d), 7.36 (1H, d), 7.55-7.61 (3H, overlapping m), 7.65 (1H, m), 7.94 (1H, m), 8.29 (1H, m), 8.45 (1H, m), 9.00 (1H, bs).

후처리

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted with a further amount of 30% MeOH in DCM (2×600 mL)
  3. concentrationthe organics were concentrated in vacuo
  4. customto afford the crude product
  5. customThe crude product was triturated with MeOH (200 mL)
  6. customsonicated for c.a
  7. filtrationThe resulting solid was collected by filtration
  8. washwashed with MeOH (2×10 mL)

출처 및 근거

ORD 기록
ord-e1afda266d91492abcd43fe9d301669f
출처 데이터셋
uspto-grants-2016_09
특허 번호
US09447076B2

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