Sodium Methoxide → (1S)-(2-Chloro-4-methoxy-6-methyl-pyrimidin-5-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine

HRID 1091927Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6](Cl)[C:5]([CH2:9][N:10]([CH3:21])[C@@H:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[C:4]([CH3:22])[N:3]=1.[CH3:23][O-:24].[Na+]>CO>[Cl:1][C:2]1[N:7]=[C:6]([O:24][CH3:23])[C:5]([CH2:9][N:10]([CH3:21])[C@@H:11]2[C:20]3[C:15](=[CH:16][CH:17]=[CH:18][CH:19]=3)[CH2:14][CH2:13][CH2:12]2)=[C:4]([CH3:22])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a flask containing (1S)-(2,4-dichloro-6-methyl-pyrimidin-5-ylmethyl)-methyl-(1,2,3,4-tetrahydro-naphthalen-1-yl)-amine (6.41 g, 19.06 mmol) is added MeOH (100 mL) and the solution is cooled to 0° C. using an ice bath. NaOMe (0.5 M, 38 mL) is added via addition funnel over 20 min. Once addition is complete, the ice bath is removed and the reaction is allowed to proceed overnight warming to room temperature. HOAc (2.0 mL) is added and the reaction mixture is allowed to stir for 10 min, followed by concentration at reduced pressure. The resulting oil is dissolved in EtOAc (100 mL) and washed sat. NaHCO3 (100 mL), brine (100 mL) and dried over Na2SO4. Flash chromatography on SiO2 using first CHCl3 followed by 20:1 hexanes:Et2O affords the title compound as a colorless oil. [mass expected (331.84); mass found (331.28)]

Workup

additionOnce addition
customthe ice bath is removed
temperaturewarming to room temperature
additionHOAc (2.0 mL) is added
concentrationfollowed by concentration at reduced pressure
dissolutionThe resulting oil is dissolved in EtOAc (100 mL)
washwashed sat. NaHCO3 (100 mL), brine (100 mL)
dry with materialdried over Na2SO4

Sources & evidence

ORD record: ord-5529c3b144f04657879ddb630dcb9e65
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129395B2

Reaction notes

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