Water → HCID 86706697, compound

HRID 1468085Notes

Reaction equation

HRID 1468085 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7]3([CH2:16][CH2:15][CH:14]([O:17][CH3:18])[CH2:13][CH2:12]3)[C:8]2=O)=[CH:4][C:3]=1[F:19].[CH3:20][C:21]([S:24]([NH2:26])=[O:25])([CH3:23])[CH3:22].O>CCOC(C)=O.[O-]CC.[Ti+4].[O-]CC.[O-]CC.[O-]CC>[Br:1][C:2]1[CH:10]=[C:9]2[C:5](=[CH:4][C:3]=1[F:19])[CH2:6][C:7]1([CH2:16][CH2:15][CH:14]([O:17][CH3:18])[CH2:13][CH2:12]1)[C:8]2=[N:26][S:24]([C:21]([CH3:23])([CH3:22])[CH3:20])=[O:25]

Participants

6

Reactant 3

HCID 962WaterHCID 3382465Tert-ButanesulfinamideHCID 58197930HCID 58197930, compound2×

Product 1

HCID 86706697HCID 86706697, compoundYield 57%

Reagents, catalysts & solvents 2

HCID 76524Titanium tetraethoxideCatalystHCID 8857Ethyl AcetateSolvent

Procedure

6′-Bromo-5′-fluoro-4-methoxyspiro[cyclohexane-1,2′-inden]-1′(3′H)-one (Intermediate 8, 2.0 g, 6.11 mmol), 2-methylpropane-2-sulfinamide (1.11 g, 9.17 mmol) and titanium ethoxide (2.52 mL, 12.2 mmol) were dissolved in 2-Me THF (31 mL) and heated to reflux for 48 h. The reaction was allowed to cool to r.t. whereafter it was diluted with EtOAc (75 mL). Water (25 mL) was added dropwise over 10 min under vigorous stirring and then the mixture was left standing without stirring for 1.5 h. The solids were filtered off and the organics were concentrated. The was purified by silica gel chromatography using a stepwise gradient of heptane/EtOAC (5:1-4:1-3:1-1:1), to give the title compound (1.5 g, 57% yield) as a diasteromer mixture in the ratio ˜4:1 (established by HPLC and NMR analysis) (1.50 g, 57% yield). The was used in the next step. 1H NMR (500 MHz, CDCl3, signals for both isomers) δ ppm 1.20-1.29 (m, 1 H) 1.30-1.41 (m, 14 H) 1.50-1.60 (m, 4 H) 1.60-1.68 (m, 1 H) 1.97-2.08 (m, 1 H) 2.08-2.20 (m, 2.5 H) 2.24-2.32 (m, 0.3 H) 2.95-3.02 (m, 2.5 H) 3.22-3.32 (m, 1 H) 3.35 (s, 0.9 H) 3.40 (s, 3 H) 3.48-3.53 (m, 0.3 H) 7.09-7.11 (m, 0.3 H) 7.13 (d, 1 H) 8.64-8.88 (m, 1 H); MS (ES+) m/z 430, 432 [M+H]+.

Workup

  1. temperatureheated
  2. temperatureto reflux for 48 h
  3. waitthe mixture was left
  4. stirringwithout stirring for 1.5 h
  5. filtrationThe solids were filtered off
  6. concentrationthe organics were concentrated
  7. customThe was purified by silica gel chromatography

Sources & evidence

ORD record
ord-ef72868882504b579f148133da6e89be
Source dataset
uspto-grants-2015_04
Patent number
US09000183B2

Reaction notes

Loading…