Tetrahydrofuran → (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

HRID 406687Notes

Reaction equation

HRID 406687 reaction equation
[CH2:1]([C@@:4]1([C:27]2[CH:32]=[CH:31][C:30]([F:33])=[CH:29][CH:28]=2)[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([C:19]3[C:20](=[O:26])[N:21]([CH3:25])[CH:22]=[CH:23][CH:24]=3)=[CH:15][CH:14]=2)[CH3:12])[CH2:6][CH2:5]1)[CH:2]=[CH2:3].C(BC(C(C)C)C)(C(C)C)C.C1C[O:48]CC1>>[F:33][C:30]1[CH:31]=[CH:32][C:27]([C@:4]2([CH2:1][CH2:2][CH2:3][OH:48])[O:9][C:8](=[O:10])[N:7]([C@H:11]([C:13]3[CH:14]=[CH:15][C:16]([C:19]4[C:20](=[O:26])[N:21]([CH3:25])[CH:22]=[CH:23][CH:24]=4)=[CH:17][CH:18]=3)[CH3:12])[CH2:6][CH2:5]2)=[CH:28][CH:29]=1

Participants

4

Reactant 3

HCID 8028TetrahydrofuranHCID 192733Bis(1,2-dimethylpropyl)boraneHCID 59635680(R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one

Product 1

HCID 59635669(R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-oneYield 30%

Procedure

A solution of (R)-6-allyl-6-(4-fluorophenyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (13.3 mg, 0.030 mmol) in dry THF (1.5 mL) was cooled to 0° C. Disiamyl borane (0.5M in THF, 5004, excess) was added. After 10 min, the mixture was warmed to rt and stirred for 1 h. The mixture was cooled to 0° C. again, quenched with water (1 mL) and NaBO3 (10 mg). The mixture was concentrated and purified by prep HPLC to afford (R)-6-(4-fluorophenyl)-6-(3-hydroxypropyl)-3-((S)-1-(4-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)phenyl)ethyl)-1,3-oxazinan-2-one (4.2 mg, 30% yield). LC-MS Method 1 tR=1.33 min, m/z=487(M+1); 1H NMR (CD3Cl) δ 7.47(dd, 1H), 7.38(m, 3H), 7.24(m, 2H), 7.07(t, 2H), 6.96(d, 2H), 6.39(t, 1H), 5.65(m, 1H), 4.26(t, 1H), 3.66(s, 3H), 2.91(m, 1H), 2.40-2.14(m, 3H), 1.54(d, 3H).

Workup

  1. temperatureThe mixture was cooled to 0° C. again
  2. customquenched with water (1 mL) and NaBO3 (10 mg)
  3. concentrationThe mixture was concentrated
  4. custompurified by prep HPLC

Sources & evidence

ORD record
ord-58714e1b21a34951b471209637fb2343
Source dataset
uspto-grants-2014_06
Patent number
US08754076B2

Reaction notes

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