Tetrahydrofuran → 4-(2-Methoxyethoxy)pyridin-2-amine

HRID 1095757Notes

Reaction equation

Cl[C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][O:11][CH3:12])[CH:5]=[CH:4][N:3]=1.O1CCCC1.C[Si]([N-:22][Si](C)(C)C)(C)C.[Li+]>Cl.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC(C1C=C(C(C)C)C(C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)=C(C(C)C)C=1)C>[CH3:12][O:11][CH2:10][CH2:9][O:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:22])[CH:7]=1

Participants

Conditions

Temperature: 60 °C

Procedure

A steady stream of nitrogen was passed through a mixture of 2-chloro-4-(2-methoxyethoxy)pyridine (50.1 g, 267 mmol), Pd2dba3 (4.89 g, 5.34 mmol), XPHOS (5.09 g, 10.7 mmol) and tetrahydrofuran (445 ml) for 10 minutes. To the resulting degassed mixture was added lithium bis(trimethylsilyl)amide (561 ml, 561 mmol). After addition, the resulting mixture was heated to 60° C. for 18 hours. The reaction was cooled to ambient temperature and diluted with 1 N hydrochloric acid (200 mL). The resulting solution was washed twice with 500 ml of methyl-tert-butyl ether. The pH of the aqueous layer was adjusted to 11 with 6 N NaOH and extracted with dichloromethane. The combined organic layers were dried over MgSO4 and concentrated under reduced pressure to yield title compound (35 g) MS APCI (+) m/z 169 (M+1) detected.

Workup

customTo the resulting degassed mixture
additionAfter addition
temperatureThe reaction was cooled to ambient temperature
washThe resulting solution was washed twice with 500 ml of methyl-tert-butyl ether
extractionextracted with dichloromethane
dry with materialThe combined organic layers were dried over MgSO4
concentrationconcentrated under reduced pressure

Sources & evidence

ORD record: ord-b81555bd8edc453fac8e2e5193cda16a
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08138181B2

Reaction notes

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