Acetic Acid → 7-amino-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one

HRID 1372505Notes

Reaction equation

[NH2:1][C:2]1[C:3]([Cl:22])=[C:4]2[C:8](=[CH:9][C:10]=1[F:11])[C:7](=O)[C:6]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:13][CH2:14][C:15](=[O:17])[CH3:16])[CH2:5]2.C(O)(=O)C.N1CCCC1>C1(C)C=CC=CC=1>[NH2:1][C:2]1[C:3]([Cl:22])=[C:4]2[C:8]([C:7]3[C:6]([CH2:18][CH2:19][CH2:20][CH3:21])([CH2:5]2)[CH2:13][CH2:14][C:15](=[O:17])[CH:16]=3)=[CH:9][C:10]=1[F:11]

Participants

Conditions

Temperature: 90 °C

Procedure

The crude diketone from step 7 (approx. 10.6 mmol) was dissolved in toluene (106 mL) and treated with acetic acid (0.606 mL, 10.6 mmol) and pyrrolidine (0.883 mL, 10.6 mmol). The resulting solution was stirred and heated in an oil bath at 90° C. for 3.5 hours. After cooling to room temperature, the mixture was filtered through a pad of silica gel and the product washed off with EtOAc. The filtrate and washings were concentrated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 4:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide 7-amino-9a-butyl-8-chloro-6-fluoro-1,2,9,9a-tetrahydro-3H-fluoren-3-one (2.7 g, 83%) as a yellow solid.

Workup

temperatureAfter cooling to room temperature
filtrationthe mixture was filtered through a pad of silica gel
washthe product washed off with EtOAc
concentrationThe filtrate and washings were concentrated under vacuum
customThe residue was purified by flash chromatography on a Biotage 40M KP-Sil column
washeluting with 4:1 hexanes-EtOAc
additionThe product containing fractions
customwere evaporated under vacuum

Sources & evidence

ORD record: ord-f8f3ec3f1a4940b6a851ffda370e9718
Source dataset: uspto-grants-2007_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07157604B2

Reaction notes

Loading…