Sodium → isopropyl 7-{(4R)-4-[(1E)-4,4-difluoro-3-oxo-4-phenylbut-1-en-1-yl]-2-oxo-1,3-oxazinan-3-yl}heptanoate

HRID 1826684Notes

Reaction equation

[CH:1]([C@H:3]1[CH2:8][CH2:7][O:6][C:5](=[O:9])[N:4]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17])=O.[Na].[F:23][C:24]([F:40])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:25](=[O:33])[CH2:26]P(=O)(OC)OC>C1COCC1.[Cl-].[Zn+2].[Cl-]>[F:23][C:24]([F:40])([C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][CH:35]=1)[C:25](=[O:33])/[CH:26]=[CH:1]/[C@H:3]1[CH2:8][CH2:7][O:6][C:5](=[O:9])[N:4]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][C:16]([O:18][CH:19]([CH3:21])[CH3:20])=[O:17]

Participants

Conditions

Temperature: 60 °C

Procedure

Horner-Emmons-Smith reaction: to a solution of isopropyl 7-[(4R)-4-formyl-2-oxo-1,3-oxazinan-3-yl]heptanoate (207 mg, 0.691 mmol) in THF (3 mL) was added Zinc chloride (0.5M in THF, 1.52 mL, 0.76 mmol, 1.1 eq) followed by the sodium salt of dimethyl (3,3-difluoro-2-oxo-3-phenylpropyl)phosphonate (270 mg, 0.898 mmol, 1.3 eq) as a solid and the mixture was heated to 60° C. o/n and concentrated. The residue was purified by column chromatography (80% ethyl acetate/hexanes) to give the desired product isopropyl 7-{(4R)-4-[(1E)-4,4-difluoro-3-oxo-4-phenylbut-1-en-1-yl]-2-oxo-1,3-oxazinan-3-yl}heptanoate as a light yellow oil. MS (+ESI): m/z 452 (M+1)+.

Workup

customHorner-Emmons-Smith reaction
concentrationconcentrated
customThe residue was purified by column chromatography (80% ethyl acetate/hexanes)

Sources & evidence

ORD record: ord-e30216b033994234909d3cba269413a7
Source dataset: uspto-grants-2006_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07053085B2

Reaction notes

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