Diisopropylamine → Methyl 6-fluoro-3,4-dihydro-4-(hydroxymethyl)-2H-benzopyran-4-carboxylate

HRID 487205Notes

Reaction equation

C(NC(C)C)(C)C.C([Li])CCC.[F:13][C:14]1[CH:15]=[CH:16][C:17]2[O:22][CH2:21][CH2:20][CH:19]([C:23]([O:25][CH3:26])=[O:24])[C:18]=2[CH:27]=1.C1C[O:31][CH2:30]C1>CCCCCC>[F:13][C:14]1[CH:15]=[CH:16][C:17]2[O:22][CH2:21][CH2:20][C:19]([CH2:30][OH:31])([C:23]([O:25][CH3:26])=[O:24])[C:18]=2[CH:27]=1

Participants

Conditions

Temperature: 0 °C

Procedure

A solution of 5 mL (0.035 mole) of diisopropylamine in 100 mL of THF was cooled to 0° C. and 22.1 mL (0.35 mole) of 1.6M butyllithium in hexane was added dropwise. After stirring for 30 minutes at 0° C. the resulting solution was cooled to -78° C. A solution of 6.2 g (0.0295 mole) of Methyl 6-fluoro-2,3-dihydro-4H-benzopyran-4-carboxylate in 20 mL of THF was then added dropwise while maintaining the temperature below -66° C. The resulting solution was stirred at -78° C. for 3 hours. Gaseous formaldehyde was then bubbled into the solution for 5 minutes. The reaction was allowed to warm to room temperature, then diluted with water and extracted with EtOAc. The EtOAc layer was dried over Na2SO4, filtered and evaporated to give 7.6 g of crude product as an oil. NMR (CDCl3) ppm (delta): 2.20-2.60 (m, 2H), 3.8 (s, 3H), 4.26 (t, 2H, J=5 Hz), 4.90 (m, 2H), 6.80-7.20 (m, 3H).

Workup

temperaturewas cooled to -78° C
temperaturewhile maintaining the temperature below -66° C
stirringThe resulting solution was stirred at -78° C. for 3 hours
customGaseous formaldehyde was then bubbled into the solution for 5 minutes
temperatureto warm to room temperature
additiondiluted with water
extractionextracted with EtOAc
dry with materialThe EtOAc layer was dried over Na2SO4
filtrationfiltered
customevaporated

Sources & evidence

ORD record: ord-733ad802029e421ebe3d68d992d4379e
Source dataset: uspto-grants-1994_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US05294635

Reaction notes

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