Triphenylphosphine → Methyl 6-[tert-butoxycarbonyl-(2-ethoxy-2-oxo-acetyl)amino]norbornane-2-carboxylate

HRID 75046Notes

Reaction equation

O[CH:2]1[CH:7]2[CH2:8][CH:4]([CH2:5][CH:6]2[C:9]([O:11][CH3:12])=[O:10])[CH2:3]1.[C:13]([O:17][C:18]([NH:20][C:21](=[O:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1COCC1>[C:13]([O:17][C:18]([N:20]([CH:2]1[CH:7]2[CH2:8][CH:4]([CH2:5][CH:6]2[C:9]([O:11][CH3:12])=[O:10])[CH2:3]1)[C:21](=[O:27])[C:22]([O:24][CH2:25][CH3:26])=[O:23])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

Conditions

Temperature: 85 °C

Procedure

To a cold (0° C.) solution of methyl 6-hydroxynorbornane-2-carboxylate, 72e, (3.2 g, 18.8 mmol) in THF (150 mL) was added ethyl 2-(tert-butoxycarbonylamino)-2-oxo-acetate (4.9 g, 22.6 mmol) and triphenylphosphine (5.9 g, 22.6 mmol) followed by dropwise addition of diisopropyl azodicarboxylate (4.5 g, 22.6 mmol). The reaction was then heated to 85° C. and maintained at that temperature for 2 days. The solvent was evaporated under reduced pressure and the crude product was purified by silica gel chromatography (0-100% EtOAc/hexanes gradient) to provide 6 g of methyl 6-(N-(tert-butoxycarbonyl)-2-ethoxy-2-oxoacetamido)bicyclo[2.2.1]heptane-2-carboxylate: LCMS 392.34 (M+Na+); 1H NMR (300 MHz, CDCl3) δ 4.26 (q, J=7.2 Hz, 2H), 4.08 (dt, J=14.3, 7.2 Hz, 1H), 3.62 (d, J=2.1 Hz, 3H), 2.72 (s, 1H), 2.42-2.26 (m, 2H), 2.08-1.80 (m, 2H), 1.80-1.51 (m, 3H), 1.45 (s, 9H), 1.38-1.25 (m, 3H).

Workup

temperaturemaintained at that temperature for 2 days
customThe solvent was evaporated under reduced pressure
customthe crude product was purified by silica gel chromatography (0-100% EtOAc/hexanes gradient)

Sources & evidence

ORD record: ord-3f67b93a23734150bdb1af034bc4ead5
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08829007B2

Reaction notes

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