Formic Acid → (7aS,11aR)-2-(2,6-difluorophenyl)-10-methyl-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3',4':4,5]pyrrolo[3,2,1-ij]quinoline

HRID 1292908Notes

Reaction equation

[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([F:8])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:16]3=[C:17]([C@@H:19]4[CH2:24][NH:23][CH2:22][CH2:21][C@@H:20]4[N:15]3[CH2:14][CH2:13][CH2:12]2)[CH:18]=1.C=O.[CH:27](O)=O.C([O-])([O-])=O.[Na+].[Na+]>O>[F:8][C:4]1[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[C:3]=1[C:9]1[CH:10]=[C:11]2[C:16]3=[C:17]([C@@H:19]4[CH2:24][N:23]([CH3:27])[CH2:22][CH2:21][C@@H:20]4[N:15]3[CH2:14][CH2:13][CH2:12]2)[CH:18]=1

Participants

Conditions

Temperature: 80 °C

Procedure

A mixture of (7aS,11aR)-2-(2,6-difluorophenyl)-5,6,7a,8,9,10,11,11a-octahydro-4H-pyrido[3′,4′:4,5]pyrrolo[3,2,1-ij]quinoline (0.050, 0.15 mmol), HCHO (0.20 mL, 2.9 mmol) and formic acid (1.0 mL, 2.9 mmol) was heated at 80° C. for 4 h and cooled to room temperature. Water (5.0 mL) was added and the solution was basified with saturated Na2CO3 until pH>8. The mixture was extracted with CH2Cl2 (3×10 mL), dried (Na2SO4) and flash column chromatography (1-5% MeOH in CHCl3) gave the title compound (0.032 g, 62%) as a white foam. 1H NMR (CDCl3, 300 MHz) δ 2.00-2.20 (m, 5H), 2.20-2.50 (m, 4H), 2.55-2.68 (m, 1H), 2.68-2.82 (m, 3H), 2.86-2.98 (m, 1H), 3.28-3.42 (m, 3H), 6.90-7.08 (m, 4H), 7.14-7.25 (m, 1H) ppm. MS (ESI): 341 (base, M+H).

Workup

temperaturecooled to room temperature
extractionThe mixture was extracted with CH2Cl2 (3×10 mL)
dry with materialdried (Na2SO4) and flash column chromatography (1-5% MeOH in CHCl3)

Sources & evidence

ORD record: ord-faaedd204bd44549aebffd87e78f6473
Source dataset: uspto-grants-2007_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07238690B2

Reaction notes

Loading…