N,N-Dimethylaniline → Tert-butyl 4-((6-chloropyrimidin-4-yl)methyl)phenylcarbamate

HRID 1993553Notes

Reaction equation

HRID 1993553 reaction equation
[ClH:1].C(N(CC)CC)C.CN(C)C1C=CC=CC=1.O=P(Cl)(Cl)Cl.[C:23]([O:27][C:28](=[O:44])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]2[CH:42]=[C:41](O)[N:40]=[CH:39][N:38]=2)=[CH:32][CH:31]=1)([CH3:26])([CH3:25])[CH3:24]>CC#N>[C:23]([O:27][C:28](=[O:44])[NH:29][C:30]1[CH:35]=[CH:34][C:33]([CH2:36][C:37]2[CH:42]=[C:41]([Cl:1])[N:40]=[CH:39][N:38]=2)=[CH:32][CH:31]=1)([CH3:26])([CH3:25])[CH3:24]

Participants

6

Reactant 4

HCID 949N,N-DimethylanilineHCID 11130Triethylamine hydrochlorideHCID 24813Phosphorus oxychlorideHCID 178452708HCID 178452708, compound

Product 1

HCID 58659459Tert-butyl 4-((6-chloropyrimidin-4-yl)methyl)phenylcarbamate

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

Triethylamine hydrochloride (0.93 g 6.60 mmol), N,N-dimethylaniline (0.8 mL, 6.60 mmol), and POCl3 (3.7 mL, 39.6 mmol, 6 equiv) are added sequentially to a solution of [4-(6-hydroxy-pyrimidin-4-ylmethyl)-phenyl]-carbamic acid tert-butyl ester (2.0 g, 6.60 mmol) in CH3CN (16.5 mL), at rt and under an argon atmosphere. The resulting yellow solution is stirred at rt for 1 h and then added to a stirred mixture of H2O/ice (1/1, v/v; 80 mL, total volume). The product is extracted in CH2Cl2 (2×200 mL). The organic phase is washed with an aqueous saturated solution of Na2CO3 (70 mL), dried (Na2SO4), filtered and concentrated in vacuo. The residue is purified by silica gel (170 g) column chromatography (CH2Cl2/Et2O, 95/5, then 90/10) to afford the title compound: ES-MS: 320.1 [M+H]+; single peak at tR=8.76 min (System 2); Rf=0.13 (CH2Cl2/Et2O, 95/5).

Workup

  1. extractionThe product is extracted in CH2Cl2 (2×200 mL)
  2. washThe organic phase is washed with an aqueous saturated solution of Na2CO3 (70 mL)
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue is purified by silica gel (170 g) column chromatography (CH2Cl2/Et2O, 95/5

Sources & evidence

ORD record
ord-cd6bd7796e1b407f9f44a9b8edc1f8be
Source dataset
uspto-grants-2010_01
Patent number
US07652022B2

Reaction notes

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