Potassium Carbonate → Tert-butyl (1-(4-chloro-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate

HRID 1529417Notes

Reaction equation

HRID 1529417 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[CH:5]=[C:4]([O:9][CH3:10])[N:3]=1.[NH:11]1[CH2:16][CH2:15][CH:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[CH2:13][CH2:12]1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C>[Cl:8][C:6]1[CH:5]=[C:4]([O:9][CH3:10])[N:3]=[C:2]([N:11]2[CH2:12][CH2:13][CH:14]([NH:17][C:18](=[O:24])[O:19][C:20]([CH3:22])([CH3:21])[CH3:23])[CH2:15][CH2:16]2)[N:7]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 7238334-(N-Boc-amino)piperidineHCID 38245092,4-Dichloro-6-methoxypyrimidine

Product 1

HCID 86709788Tert-butyl (1-(4-chloro-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamateYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2,4-dichloro-6-methoxypyrimidine (5.0 g, 28.0 mmol) and tert-butyl piperidin-4-ylcarbamate (5.6 g, 28.0 mmol) in DMF (50 mL) was added K2CO3 (7.74 g, 56.0 mmol) and the mixture was stirred at RT for 6 h. The reaction was quenched with water and the suspension was filtered, washed with water and dried. The crude was purified with silica gel chromatography (eluting with 20% EtOAc in petroleum ether) to give tert-butyl (1-(4-chloro-6-methoxypyrimidin-2-yl)piperidin-4-yl)carbamate 276a (6.0 g, 73% yield). MS (ESI, pos. ion) m/z: 342.8 (M+1); 1H-NMR (400 MHz, CDCl3): δ ppm 5.97 (s, 1H), 4.64 (d, 2 H, J=13.2 Hz), 4.49 (brs, 1H), 3.88 (s, 3H), 3.04 (t, 2 H, J=11.6 Hz), 2.03 (d, 2 H, J=10.4 Hz), 1.57 (s, 3H), 1.46 (s, 9H). And tert-butyl (1-(2-chloro-6-methoxypyrimidin-4-yl)piperidin-4-yl)carbamate 276b (1.0 g, 12% yield). MS (ESI, pos. ion) m/z: 343.1 (M+1); 1H-NMR (400 MHz, CDCl3): δ ppm 5.70 (s, 1H), 4.49 (brs, 1H), 4.22 (d, 2 H, J=12.4 Hz), 3.91 (s, 3H), 2.96-3.00 (m, 2H), 2.03 (d, 2 H, J=8.4 Hz), 1.45 (s, 9H), 1.3-1.39 (m, 2H).

Workup

  1. customThe reaction was quenched with water
  2. filtrationthe suspension was filtered
  3. washwashed with water
  4. customdried
  5. customThe crude was purified with silica gel chromatography (eluting with 20% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-b6fa3aa7e7ef49809a3e257c34116b65
Source dataset
uspto-grants-2015_07
Patent number
US09090593B2

Reaction notes

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