tert-Butanol → HCID 86729618, compound

HRID 2284891Notes

Reaction equation

HRID 2284891 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=1.C(O)(C)(C)C.C(N(CC)CC)C.[NH2:25][C@H:26]1[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]1>ClC(Cl)C.CCOC(C)=O.CCCCCC.[Cl-].[Zn+2].[Cl-]>[Cl:8][C:6]1[C:5]([C:9]([F:12])([F:11])[F:10])=[CH:4][N:3]=[C:2]([NH:25][C@H:26]2[CH2:31][CH2:30][CH2:29][N:28]([C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33])[CH2:27]2)[N:7]=1

Participants

9

Reactant 4

HCID 6386tert-ButanolHCID 8471TriethylamineHCID 1501975tert-butyl (3S)-3-aminopiperidine-1-carboxylateHCID 27827742,4-Dichloro-5-(trifluoromethyl)pyrimidine

Product 1

HCID 86729618HCID 86729618, compoundYield 57.1%

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 63651,1-DichloroethaneSolventHCID 8058HexaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2,4-dichloro-5-(trifluoromethyl)pyrimidine (5 g, 23 mmol) in dichloroethane: t-butanol (50 ml, 1:1) was added dry zinc chloride (3.7 g, 27 mmol) and triethylamine (2.52 g, 25 mmol), and the mixture was stirred at rt for 1 h (pH should not be >7). To this mixture, (S)-tert-butyl 3-aminopiperidine-1-carboxylate (4.9 g, 25 mmol) was added and stirring continued at rt for 16 h. TLC showed formation of the major compound (0.2 Rf) and a minor other isomer (0.25 Rf) and ˜10% starting material in 15% EtOAc: hexane solvent system. Solvents were evaporated, and crude was diluted with ice cold water (50 mL) and stirred for 5 min at rt to get a pale yellow gummy mass. The crude pale yellow gummy mass (6 g) was taken in 60 mL hexane and stirred for 10 min at rt to get a solid which was immediately filtered to get the pure desired compound (5 g, 57%). MS m/z: 381.1 (ES+, M+H).

Workup

  1. stirringstirring
  2. waitcontinued at rt for 16 h
  3. customSolvents were evaporated
  4. additioncrude was diluted with ice cold water (50 mL)
  5. stirringstirred for 5 min at rt
  6. customto get a pale yellow gummy mass
  7. stirringstirred for 10 min at rt
  8. customto get a solid which
  9. filtrationwas immediately filtered

Sources & evidence

ORD record
ord-7feac5b84b0645f2b23f8d7dd8582168
Source dataset
uspto-grants-2015_09
Patent number
US09145387B2

Reaction notes

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