Methyl iodide → 3-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl ester

HRID 1946126Notes

Reaction equation

HRID 1946126 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:15]2[N:16]([CH3:31])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([Cl:30])[N:18]=3)([OH:14])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[H-].[Na+].I[CH3:35]>C1COCC1.C1OCCOCCOCCOCCOC1>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH2:11][C:10]([C:15]2[N:16]([CH3:31])[C:17]3[C:22]([N:23]=2)=[C:21]([N:24]2[CH2:29][CH2:28][O:27][CH2:26][CH2:25]2)[N:20]=[C:19]([Cl:30])[N:18]=3)([O:14][CH3:35])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 59605825tert-butyl 3-(2-chloro-9-methyl-6-morpholino-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylate

Product 1

HCID 596053523-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl esterYield 92%

Reagents, catalysts & solvents 2

HCID 3633615-Crown-5CatalystHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(2-chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-hydroxypiperidine-1-carboxylic acid tert-butyl ester (4.54 g, 10.02 mmol) in THF (100 mL) was added NaH (481 mg, 12.02 mmol, 60% dispersion in mineral oil) and the mixture allowed to stir for 5 min before the addition of iodomethane (750 μL, 12.02 mmol) and 15-Crown-5 (10 drops). The resulting mixture was allowed to stir for 2.5 h then concentrated in vacuo. The resulting residue was partitioned between EtOAc and H2O and the aqueous layer further extracted with 2-methyl THF. The combined organic phases were dried (Na2SO4) and concentrated in vacuo affording 3-(2-Chloro-9-methyl-6-morpholin-4-yl-9H-purin-8-yl)-3-methoxypiperidine-1-carboxylic acid tert-butyl ester (4.30 g, 92%). LCMS (method A): RT 4.05 min, [M+H]+ 467.2

Workup

  1. concentrationthen concentrated in vacuo
  2. customThe resulting residue was partitioned between EtOAc and H2O
  3. extractionthe aqueous layer further extracted with 2-methyl THF
  4. dry with materialThe combined organic phases were dried (Na2SO4)
  5. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0ac2250599a845b1b6b4a1add42d659d
Source dataset
uspto-grants-2013_03
Patent number
US08394796B2

Reaction notes

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