Oxygen → (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(6-methoxypyridin-3-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-one

HRID 884364Notes

Reaction equation

HRID 884364 reaction equation
[CH3:1][O:2][C:3]1[N:8]=[CH:7][C:6](B(O)O)=[CH:5][CH:4]=1.[F-].[K+].OC(C(F)(F)F)=O.[OH:21][C:22]([CH3:44])([CH3:43])[CH2:23][C@@:24]1([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=2)[O:29][C:28](=[O:30])[N:27]([C@H:31]2[CH2:36][CH2:35][CH2:34][NH:33][CH2:32]2)[CH2:26][CH2:25]1.O=O>C(#N)C.CC([O-])=O.CC([O-])=O.[Cu+2]>[OH:21][C:22]([CH3:44])([CH3:43])[CH2:23][C@@:24]1([C:37]2[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=2)[O:29][C:28](=[O:30])[N:27]([C@H:31]2[CH2:36][CH2:35][CH2:34][N:33]([C:6]3[CH:7]=[N:8][C:3]([O:2][CH3:1])=[CH:4][CH:5]=3)[CH2:32]2)[CH2:26][CH2:25]1

Participants

7

Reactant 4

HCID 977Oxygen2×HCID 522689Potassium FluorideHCID 2734368(6-Methoxypyridin-3-yl)boronic acidHCID 86653637(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one TFA salt

Product 1

HCID 67019849(S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(6-methoxypyridin-3-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-oneYield 76%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
85 °C

Procedure

A suspension of 6-methoxypyridin-3-ylboronic acid (4 mg, 1.5equiv), Cu(OAc)2 (1 mg, cat. amount), potassium fluoride (1.1 mg, 1.05 equiv), and powdered activated 4 Å Molecular Sieves (15 mg) in acetonitrile (1.5 mL) was stirred in a test tube at ambient conditions for 10 min. A solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one TFA salt (6 mg, 0.018 mmol) in acetonitrile (1 mL) was added. The test tube was sealed with a septum and a balloon of oxygen gas was attached to maintain the oxygen atmosphere. The mixture was heated overnight at 85° C. LC-MS found the product peak. The mixture was filtered and purified by prep HPLC to afford (S)-6-(2-hydroxy-2-methylpropyl)-3-((S)-1-(6-methoxypyridin-3-yl)piperidin-3-yl)-6-phenyl-1,3-oxazinan-2-one (4.5 mg, 76% yield). LC-MS Method 1 tR=1.37 min, m/z=440(M+1); 1H NMR (CD3OD) 7.82(m, 2H), 7.43-7.29(m, 5H), 7.11(m, 1H), 4.14(m, 1H), 4.00(s, 3H), 3.56(t, 1H), 2.77(m, 3H), 2.52(m, 2H), 2.19(s, 2H), 1.23(s, 3H), 0.95(s, 3H).

Workup

  1. customThe test tube was sealed with a septum
  2. filtrationThe mixture was filtered
  3. custompurified by prep HPLC

Sources & evidence

ORD record
ord-d1ad1679109f4831ad3b0da91e1fe938
Source dataset
uspto-grants-2012_08
Patent number
US08242111B2

Reaction notes

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