Chloroiodomethane → (R)-N-((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide

HRID 1850154Notes

Reaction equation

HRID 1850154 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][S@@:15]([C:17]([CH3:20])([CH3:19])[CH3:18])=[O:16])[CH3:13])=[C:8]([F:21])[CH:7]=1)=[CH2:5])[CH3:2].Cl[CH2:23]I.C([Zn]CC)C.[NH4+].[Cl-]>C1(C)C=CC=CC=1.CO.C(Cl)Cl>[CH2:1]([O:3][C:4]1([C:6]2[CH:11]=[CH:10][C:9]([C@@H:12]([NH:14][S@@:15]([C:17]([CH3:19])([CH3:18])[CH3:20])=[O:16])[CH3:13])=[C:8]([F:21])[CH:7]=2)[CH2:23][CH2:5]1)[CH3:2]

Participants

7

Reactant 4

HCID 11644ChloroiodomethaneHCID 25517Ammonium ChlorideHCID 86730184(R)-N-((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamideHCID 178418750HCID 178418750, compound

Product 1

HCID 86730185(R)-N-((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamideYield 28.2%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

To a round bottom flask containing (R)—N—((S)-1-(4-(1-ethoxyvinyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (0.49 g, 1.56 mmol) and chloroiodomethane (1.14 mL, 15.6 mmol) in toluene (15 mL) at 0° C. under argon was added diethylzinc (1.0M in hexanes) (15.6 mL, 15.6 mmol). Reaction mixture allowed to warm to room temperature and stirred for 1 hour. Reaction mixture was cooled to 0° C. in an ice bath and to the cold reaction mixture was slowly added a saturated solution of NH4Cl. The aqueous mixture was extracted with EtOAc. Organic phases combined, washed with water, brine, dried (Na2SO4), filtered and concentrated onto silica gel. Silica gel column chromatography (MeOH/CH2Cl2 0 to 10%) provided (R)—N—((S)-1-(4-(1-ethoxycyclopropyl)-2-fluorophenyl)ethyl)-2-methylpropane-2-sulfinamide (145 mg, 0.44 mmol, 28% yield) as a viscous brown oil. 1H NMR (300 MHz, CDCL3) δ 0.93-0.99 (m, 2H) 1.14-1.20 (m, 3H) 1.21 (s, 9H) 1.22-1.27 (m, 2H) 1.57-1.61 (m, 4H) 3.35 (d, J=4.98 Hz, 1H) 3.45 (q, J=7.07 Hz, 2H) 4.77-4.87 (m, 1H) 6.98 (dd, J=7.58, 1.43 Hz, 3H) 7.00-7.03 (m, 4H) 7.28-7.32 (m, 1H). LCMS m/z 328.1 (M+H)+, Rt 0.95 min.

Workup

  1. customReaction mixture
  2. customReaction mixture
  3. temperaturewas cooled to 0° C. in an ice bath and to the cold reaction mixture
  4. extractionThe aqueous mixture was extracted with EtOAc
  5. washwashed with water, brine
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated onto silica gel

Sources & evidence

ORD record
ord-29a9495b58d94553b5708036a658763b
Source dataset
uspto-grants-2015_02
Patent number
US08957068B2

Reaction notes

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