Sodium Hydroxide → Benzyl 3-(2-amino-6-chloropyrimidin-4-yl)piperidine-1-carboxylate

HRID 16429Notes

Reaction equation

[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4](O)[N:3]=1.C(N(CC)C(C)C)(C)C.P(Cl)(Cl)([Cl:36])=O.[OH-].[Na+]>C(#N)C.[Cl-].C([N+](CC)(CC)CC)C1C=CC=CC=1>[NH2:1][C:2]1[N:7]=[C:6]([CH:8]2[CH2:13][CH2:12][CH2:11][N:10]([C:14]([O:16][CH2:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[O:15])[CH2:9]2)[CH:5]=[C:4]([Cl:36])[N:3]=1

Participants

Conditions

Temperature: 0 °C

Procedure

4.14 g (12.60 mmol) of benzyl 3-(2-amino-6-hydroxypyrimidin-4-yl)piperidine-1-carboxylate (from example LXXI) are suspended in 150 ml of acetonitrile. 3.29 ml (18.91 mmol) of N,N-diisopropylethylamine and 0.57 g (2.52 mmol) of benzyltriethylammonium chloride are added successively. The mixture is cooled to 0° C. At 0° C., 4.7 ml (50.43 mmol) of phosphoryl chloride are then slowly added dropwise. The mixture is stirred at room temperature for 18 hours. For work-up, the reaction solution is cooled to 0° C. and carefully added dropwise to ice water (150 ml). The aqueous suspension is neutralized using a 45% strength sodium hydroxide solution and extracted three times with ethyl acetate (in each case 70 ml). The organic phase is dried over anhydrous magnesium sulfate and concentrated. The residue is purified on a silica gel column using dichloromethane/methanol 30:1. This gives 2.80 g (64% of theory) of product.

Workup

temperatureFor work-up, the reaction solution is cooled to 0° C.
extractionextracted three times with ethyl acetate (in each case 70 ml)
dry with materialThe organic phase is dried over anhydrous magnesium sulfate
concentrationconcentrated
customThe residue is purified on a silica gel column

Sources & evidence

ORD record: ord-45753a7c23954586a5ef50bf13e865e0
Source dataset: uspto-grants-2010_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07737153B2

Reaction notes

Loading…