Hydrochloric Acid → (S)-3-((S)-1-(3-fluoropyridin-2-yl)piperidin-3-yl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one

HRID 884363Notes

Reaction equation

HRID 884363 reaction equation
OC(C(F)(F)F)=O.[OH:8][C:9]([CH3:31])([CH3:30])[CH2:10][C@@:11]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[O:16][C:15](=[O:17])[N:14]([C@H:18]2[CH2:23][CH2:22][CH2:21][NH:20][CH2:19]2)[CH2:13][CH2:12]1.F[C:33]1[C:38]([F:39])=[CH:37][CH:36]=[CH:35][N:34]=1.CCN(C(C)C)C(C)C.Cl>CO.C(O)CC>[F:39][C:38]1[C:33]([N:20]2[CH2:21][CH2:22][CH2:23][C@H:18]([N:14]3[CH2:13][CH2:12][C@:11]([CH2:10][C:9]([OH:8])([CH3:31])[CH3:30])([C:24]4[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=4)[O:16][C:15]3=[O:17])[CH2:19]2)=[N:34][CH:35]=[CH:36][CH:37]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 27831762,3-DifluoropyridineHCID 86653637(S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one TFA salt

Product 1

HCID 44511971(S)-3-((S)-1-(3-fluoropyridin-2-yl)piperidin-3-yl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-oneYield 50%

Reagents, catalysts & solvents 1

HCID 19884402MeOH n-PropanolSolvent

Procedure

A solution of (S)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-3-((S)-piperidin-3-yl)-1,3-oxazinan-2-one TFA salt (12 mg, 0.036 mmol), 2,3-difluoropyridine (6 mg, 2equiv), and i-Pr2NEt (30 μL, 5 equiv) in 1:6 MeOH/n-Propanol (2 mL) was heated in the microwave oven for 15 min. at 150° C. After being cooled to rt, the mixture was acidified with 5% aq HCl solution and purified by prep HPLC to afford (S)-3-((S)-1-(3-fluoropyridin-2-yl)piperidin-3-yl)-6-(2-hydroxy-2-methylpropyl)-6-phenyl-1,3-oxazinan-2-one (5.8 mg, 50% yield). LC-MS Method 1 tR=1.51 min, m/z=428(M+1); 1H NMR (CD3OD) 7.92(dd, 1H), 7.51-7.28(m, 6H), 6.88(m, 1H), 4.10(m, 1H), 3.91(m, 2H), 3.06(td, 1H), 2.51(m, 2H), 2.19(s, 2H), 1.24(s, 3H), 0.94(s, 3H).

Workup

  1. custompurified by prep HPLC

Sources & evidence

ORD record
ord-601257f8ebb448e49b2a350cb086737d
Source dataset
uspto-grants-2012_08
Patent number
US08242111B2

Reaction notes

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