Water → Trifluoroacetic acid

HRID 1426039Notes

Reaction equation

HRID 1426039 reaction equation
[OH:1][C:2]([CH3:35])([CH3:34])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16](B3OC(C)(C)C(C)(C)O3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39].Br[C:44]1[CH:45]=[N:46][C:47]([N:50]2[CH2:53][CH:52]([OH:54])[CH2:51]2)=[N:48][CH:49]=1.C([O-])([O-])=O.[Cs+].[Cs+].O>O1CCOCC1>[OH:1][C:2]([CH3:34])([CH3:35])[CH2:3][C@@:4]1([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:14]=[CH:15][C:16]([C:44]3[CH:45]=[N:46][C:47]([N:50]4[CH2:53][CH:52]([OH:54])[CH2:51]4)=[N:48][CH:49]=3)=[CH:17][CH:18]=2)[CH3:12])[CH2:6][CH2:5]1.[F:36][C:37]([F:42])([F:41])[C:38]([OH:40])=[O:39]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 59532385(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-1-(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)ethyl)-1,3-oxazinan-2-oneHCID 67998185HCID 67998185, compound

Product 2

HCID 6422Trifluoroacetic acidHCID 70652127HCID 70652127, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
110 °C

Procedure

A heavy-walled glass vial was charged with (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-{(S)-1-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethyl}-1,3-oxazinan-2-one (13 mg), 1-(5-bromopyrimidin-2-yl)azetidin-3-ol trifluoroacetic acid salt (18 mg), Cs2CO3 (18 mg), water (0.1 mL), and 1,4-dioxane (1 mL). The mixture was sparged with N2 for 10 min before PdCl2[1,1′-bis(diphenylphosphino)ferrocene] (2 mg) was added. The mixture was sparged with N2 for 10 min and then heated in a microwave oven at 110° C. for 30 min. After cooling to room temperature, the reaction mixture was purified by preparative HPLC to afford the title compound as its trifluoroacetic acid salt as an oil. Yield: 12.1 mg (89% of theory); LC (method 5): tR=1.3 min; Mass spectrum (ESI+): m/z=503 [M+H]+; 1H NMR (CD3OD) δ 0.95 (s, 3H), 1.26 (s, 3H), 1.56 (d, 3H), 2.16 (s, 2H), 2.23 (m, 1H), 2.47 (m, 2H), 3.05 (m, 1H), 4.07 (m, 2H), 4.49 (m, 2H), 4.73 (m, 1H), 5.57 (q, 1H), 7.09 (d, 2H), 7.25-7.40 (7H), 8.63 (s, 2H).

Workup

  1. customThe mixture was sparged with N2 for 10 min before PdCl2[1,1′-bis(diphenylphosphino)ferrocene] (2 mg)
  2. additionwas added
  3. customThe mixture was sparged with N2 for 10 min
  4. temperatureAfter cooling to room temperature
  5. customthe reaction mixture was purified by preparative HPLC

Sources & evidence

ORD record
ord-b8f49eeb211741bd8a2073b91d4dc0bb
Source dataset
uspto-grants-2015_01
Patent number
US08933072B2

Reaction notes

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