Diiodomethane → HCID 59458553, compound

HRID 1874307Notes

Reaction equation

HRID 1874307 reaction equation
[CH2:1]([Zn]CC)C.CCCCCC.FC(F)(F)C(O)=O.ICI.[F:22][C:23]1[CH:28]=[CH:27][C:26]([C@@:29]([NH:51][S@:52]([C:54]([CH3:57])([CH3:56])[CH3:55])=[O:53])([C:37]2[CH:42]=[C:41]([O:43][C:44]([F:49])([F:48])[CH:45]([F:47])[F:46])[CH:40]=[C:39]([F:50])[CH:38]=2)[CH2:30][C:31]2[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=2)=[CH:25][C:24]=1[O:58][CH:59]=[CH2:60]>C(Cl)Cl>[CH:59]1([O:58][C:24]2[CH:25]=[C:26]([C@@:29]([NH:51][S@:52]([C:54]([CH3:56])([CH3:55])[CH3:57])=[O:53])([C:37]3[CH:42]=[C:41]([O:43][C:44]([F:48])([F:49])[CH:45]([F:46])[F:47])[CH:40]=[C:39]([F:50])[CH:38]=3)[CH2:30][C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[CH:27]=[CH:28][C:23]=2[F:22])[CH2:1][CH2:60]1

Participants

7

Reactant 5

HCID 6346DiiodomethaneHCID 6422Trifluoroacetic acidHCID 8058HexaneHCID 59458450(S)-N-((R)-1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamideHCID 178418750HCID 178418750, compound

Product 1

HCID 59458553HCID 59458553, compoundYield 71%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent5×

Procedure

To an oven-dried 3-necked 25 mL RB flask under nitrogen was added CH2Cl2 (3.5 mL) and 1 M diethylzinc solution in hexane (3.43 mL, 3.43 mmol). The flask was cooled in an ice-bath and a solution of trifluoroacetic acid (0.391 g, 3.43 mmol) in CH2Cl2 (1 mL) was added dropwise via syringe. After stirring for 15 min, a solution of diiodomethane (0.918 g, 3.43 mmol) in CH2Cl2 (1 mL) was added. The reaction mixture was stirred at rt for 15 min, followed by addition of (S)—N—((R)-1-(4-fluoro-3-(vinyloxy)phenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide (0.495 g, 0.87 mmol) in CH2Cl2 (1 mL). The reaction mixture was allowed to warm to rt and stirred for 4 h. The reaction mixture was diluted with CH2Cl2 and washed successively with sat. sodium bicarbonate, water, sat. NaCl, dried over MgSO4, filtered and concentrated under reduced pressure. The residue was purified by ISCO using a gradient of 5-70% EtOAc/hexane as eluent to yield (S)—N—((R)-1-(3-cyclopropoxy-4-fluorophenyl)-1-(3-fluoro-5-(1,1,2,2-tetrafluoroethoxy)phenyl)-2-phenylethyl)-2-methylpropane-2-sulfinamide as a white foam (0.347 g, 71% yield). HPLC: RT=3.668 min [M+H] 586.3 (Phenomenex Luna C18 5μ column, eluting with 10-90% aqueous acetonitrile containing 0.1% trifluoroacetic acid over a 4 minute gradient, monitoring at 220 nm). 1H NMR (CDCl3) ppm 7.2-7.05 (m, 6H), 6.91 (d, J=6.6 Hz, 2H), 6.83 (d, J=8.4 Hz, 1H), 6.71 (m, 2H), 5.84 (t, J=53.1 Hz, 1H), 4.21 (s, 1H), 3.99 (d, J=12.3 Hz, 1H), 3.62 (m, 1H), 3.56 (d, J=12.8 Hz, 1H), 1.22 (s, 9H), 0.72-0.65 (m, 4H).

Workup

  1. temperatureThe flask was cooled in an ice-bath
  2. stirringThe reaction mixture was stirred at rt for 15 min
  3. stirringstirred for 4 h
  4. washwashed successively with sat. sodium bicarbonate, water, sat. NaCl
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by ISCO

Sources & evidence

ORD record
ord-89f3438595014a1791c5a3fbe4ca3814
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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