Dichloromethane → 4-(2-Tert-butylsilyloxypropan-2-yl)-6-chloropyridin-2-amine

HRID 1814005Notes

Reaction equation

HRID 1814005 reaction equation
[Si](O[CH2:9][C:10]1[CH:15]=[C:14](Cl)[N:13]=[C:12]([NH:17]C(=O)OC(C)(C)C)[CH:11]=1)(C(C)(C)C)(C)C.FC(F)(F)S([O:30][Si:31]([C:34]([CH3:37])([CH3:36])[CH3:35])(C)C)(=O)=O.[CH:40](N(C(C)C)CC)(C)C.[CH2:49]([Cl:51])Cl>>[C:34]([SiH2:31][O:30][C:15]([CH3:14])([CH3:40])[C:10]1[CH:9]=[C:49]([Cl:51])[N:13]=[C:12]([NH2:17])[CH:11]=1)([CH3:37])([CH3:36])[CH3:35]

Participants

5

Reactant 4

HCID 6344DichloromethaneHCID 81531DiisopropylethylamineHCID 123564tert-Butyldimethylsilyl trifluoromethanesulphonate2×HCID 86588266tert-Butyl 4-({[tert-butyl(dimethyl)silyl]oxy}methyl)-6-chloropyridin-2-ylcarbamate

Product 1

HCID 1317248184-(2-Tert-butylsilyloxypropan-2-yl)-6-chloropyridin-2-amine

Conditions

Temperature
0 °C

Procedure

[4-(tert-Butyl-dimethyl-silanyloxymethyl)-6-chloro-pyridin-2-yl]-carbamic acid tert-butyl ester (11-4, 0.885 g, 2.37 mmol) was dissolved in 5 mL DCM in a flame dried flask under N2. The solution was cooled to 0° C. and tert-butyldimethylsilyl trifluoromethanesulfonate (1.09 mL, 4.75 mmol) was added. After 3 hours the reaction was warmed to room temperature and additional TBSOTf (0.545 mL, 2.37 mL) was added and the reaction was stirred overnight. Diisopropylethylamine (1.65 mL, 9.49 mmol) was added and after 10 minutes the reaction was quenched by the addition of saturated NaHCO3 (aq). The aqueous phase was extracted 3× with DCM. The combined organic extracts were dried over Na2SO4, filtered and concentrated. Purification by flash column chromatography (9:1 hex/EA) afforded a primary product which was not the desired product. This residue was dissolved in ˜25 mL MeOH and silica (˜5 g) was added. Over the course of 3 days with stirring this primary product partially converted to desired 11-5. To the reaction was added 0.5 mL HOAc and the remaining material quickly converted. The silica was filtered off, washing with MeOH and the filtrates were concentrated in vacuo to afford the titled product, 11-5. 1H NMR (CDCl3) δ 6.59 (s, 1H), 6.38 (s, 1H4.60 (s, 2H), 4.52 (bs, 2H), 0.94 (s, 9H), 0.11 (s, 6H).

Workup

  1. customdried flask under N2
  2. temperatureAfter 3 hours the reaction was warmed to room temperature
  3. customwas quenched by the addition of saturated NaHCO3 (aq)
  4. extractionThe aqueous phase was extracted 3× with DCM
  5. dry with materialThe combined organic extracts were dried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customPurification by flash column chromatography (9:1 hex/EA)
  9. customafforded a primary product which

Sources & evidence

ORD record
ord-7d3332ca948c486b828cfc1628f90982
Source dataset
uspto-grants-2005_04
Patent number
US06875767B2

Reaction notes

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