Methylamine → (S)-ethyl 2-tert-butoxy-2-(7-fluoro-3-methyl-6-(methylcarbamoyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

HRID 514107Notes

Reaction equation

HRID 514107 reaction equation
[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([F:24])=[C:17](Cl)[CH:18]=2)[C:13]=1[O:25][S:26]([C:29]([F:32])([F:31])[F:30])(=[O:28])=[O:27])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2].CN.C1[CH2:39][O:38]CC1.[CH2:40]([N:42](CC)CC)C>C(OCC)(=O)C.[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[C-]#[O+].[Mo].CC(C1C=C(C(C)C)C(C2C(P(C3CCCCC3)C3CCCCC3)=C(OC)C=CC=2OC)=C(C(C)C)C=1)C.C1C=[C-]C(CCN)=CC=1.Cl[Pd+].C1(C)C=CC=CC=1>[C:1]([O:5][C@@H:6]([C:12]1[C:21]([CH3:22])=[CH:20][C:19]2[C:14](=[CH:15][C:16]([F:24])=[C:17]([C:39](=[O:38])[NH:42][CH3:40])[CH:18]=2)[C:13]=1[O:25][S:26]([C:29]([F:32])([F:31])[F:30])(=[O:28])=[O:27])[C:7]([O:9][CH2:10][CH3:11])=[O:8])([CH3:4])([CH3:3])[CH3:2]

Participants

9

Reactant 4

HCID 6329MethylamineHCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 86691553(S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate

Product 1

HCID 86691558(S)-ethyl 2-tert-butoxy-2-(7-fluoro-3-methyl-6-(methylcarbamoyl)-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetateYield 13.9%

Reagents, catalysts & solvents 4

HCID 98885Molybdenum carbonyl (Mo(CO)6)CatalystHCID 25112666BrettPhos PalladacycleCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

A Smith process vial was charged with (S)-ethyl 2-tert-butoxy-2-(6-chloro-7-fluoro-3-methyl-1-(trifluoromethylsulfonyloxy)naphthalen-2-yl)acetate (131.8 mg, 0.263 mmol), 2 M methylamine in THF (0.66 mL, 1.32 mmol), molybdenum hexacarbonyl (0.069 g, 0.263 mmol), BrettPhos Palladacycle (29 mg, 0.0395 mmol), and triethylamine (0.128 mL, 0.921 mmol). Toluene (1.5 mL) was added and mixture was heated in microwave at 140° C. for 1.5 hour. The reaction mixture was diluted with ethyl acetate, washed brine, dried (MgSO4), filtered, concentrated and purified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexanes) to give an off-white solid (19.2 mg). LCMS-ESI+ (m/z): [M+H]+ calcd for C22H26F4NO7S: 524.5; Found: 524.0.

Workup

  1. washwashed brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. custompurified by flash column chromatography (silica gel, 0 to 50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-6441d4f8f2a74b48a4ab09291605ee4a
Source dataset
uspto-grants-2015_08
Patent number
US09102614B2

Reaction notes

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