Tetrahydrofuran → (R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

HRID 1848544Notes

Reaction equation

HRID 1848544 reaction equation
[N:1]([C@H:4]([C:24]1[C:25]([CH3:34])=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[O:28][CH2:27]2)[CH2:5][N:6]1[CH2:23][CH2:22][C:9]2([C:13](=[O:14])[N:12]([C:15]3[CH2:16][O:17][C:18](=[O:21])[C:19]=3[CH3:20])[CH2:11][CH2:10]2)[CH2:8][CH2:7]1)=[N+]=[N-].O1CCCC1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O>[NH2:1][C@H:4]([C:24]1[C:25]([CH3:34])=[C:26]2[C:30](=[CH:31][CH:32]=1)[C:29](=[O:33])[O:28][CH2:27]2)[CH2:5][N:6]1[CH2:7][CH2:8][C:9]2([C:13](=[O:14])[N:12]([C:15]3[CH2:16][O:17][C:18](=[O:21])[C:19]=3[CH3:20])[CH2:11][CH2:10]2)[CH2:22][CH2:23]1

Participants

5

Reactant 3

HCID 8028TetrahydrofuranHCID 11776TriphenylphosphineHCID 86709529(R)-8-(2-azido-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Product 1

HCID 72948650(R)-8-(2-amino-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of (R)-8-(2-azido-2-(4-methyl-1-oxo-1,3-dihydroisobenzofuran-5-yl)ethyl)-2-(4-methyl-5-oxo-2,5-dihydrofuran-3-yl)-2,8-diazaspiro[4.5]decan-1-one (250 mg, 0.54 mmol) in a mixed solvent of tetrahydrofuran and water (v:v, 12:1, 20 mL) was added triphenylphosphine (283 mg, 1.08 mmol) under nitrogen atmosphere. The reaction mixture was stirred at room temperature for 18 h. The solvent was removed by evaporation and the residue was purified by preparative TLC (dichloromethane: methanol=10:1) to afford the title compound. 1H NMR (400 MHz, Methanol-d4): δ 7.80 (d, J=8.0 Hz, 1H), δ 7.66 (d, J=8.0 Hz, 1H), 5.40 (s, 2H), 5.24 (s, 2H), 4.73 (dd, J=4.0 Hz, 8.8 Hz, 1H), 4.09 (t, J=6.8 Hz, 2H), 3.30-3.21 (m, 1H), 2.98-2.91 (m, 1H), 2.87-2.81 (m, 1H), 2.70-2.66 (m, 1H), 2.55-2.47 (m, 2H), 2.40 (s, 3H), 2.18-2.07 (m, 4H), 2.00 (s, 3H), 1.74-1.68 (m, 2H). MS-ESI (m/z): 440 (M+1)+.

Workup

  1. customThe solvent was removed by evaporation
  2. customthe residue was purified by preparative TLC (dichloromethane: methanol=10:1)

Sources & evidence

ORD record
ord-2096fc0c282247e2bb674c82d15fb5af
Source dataset
uspto-grants-2015_02
Patent number
US08952166B2

Reaction notes

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