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

HRID 63359

Reaction equation

HRID 63359 reaction equation
[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

Participants

8

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
55 °C

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-e1afda266d91492abcd43fe9d301669f
Source dataset
uspto-grants-2016_09
Patent number
US09447076B2

Linked notes

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