Ethyl Bromide → 2-Ethyl-9-(4-isopropoxy-3-methyl-benzoyl)-4-phenyl-5-oxa-2,9-diazaspiro[5.5]undecan-3-one

HRID 73045Notes

Reaction equation

HRID 73045 reaction equation
[CH:1]([O:4][C:5]1[CH:30]=[CH:29][C:8]([C:9]([N:11]2[CH2:16][CH2:15][C:14]3([CH2:21][NH:20][C:19](=[O:22])[CH:18]([C:23]4[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=4)[O:17]3)[CH2:13][CH2:12]2)=[O:10])=[CH:7][C:6]=1[CH3:31])([CH3:3])[CH3:2].[H-].[Na+].Br[CH2:35][CH3:36]>C1COCC1>[CH2:35]([N:20]1[C:19](=[O:22])[CH:18]([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[O:17][C:14]2([CH2:15][CH2:16][N:11]([C:9](=[O:10])[C:8]3[CH:29]=[CH:30][C:5]([O:4][CH:1]([CH3:3])[CH3:2])=[C:6]([CH3:31])[CH:7]=3)[CH2:12][CH2:13]2)[CH2:21]1)[CH3:36]

Participants

5

Reactant 3

HCID 6332Ethyl BromideHCID 24758Sodium hydrideHCID 68291526HCID 68291526, compound

Product 1

HCID 665469782-Ethyl-9-(4-isopropoxy-3-methyl-benzoyl)-4-phenyl-5-oxa-2,9-diazaspiro[5.5]undecan-3-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-(4-isopropoxy-3-methyl-benzoyl)-8-phenyl-7-oxa-3,10-diazaspiro[5.5]undecan-9-one (65 mg, 0.15 mmol) in THF (1 mL) at 0° C. was added NaH (6 mg, 0.15 mmol) and the reaction mixture was stirred for 30 minutes. Bromoethane (34 mg, 23 μL, 0.31 mmol) was added and the reaction mixture was stirred at room temperature for 16 hours. The reaction mixture was concentrated in vacuo and purified by silica gel column chromatography using 0-100% EtOAc/DCM as eluent to give 2-ethyl-9-(4-isopropoxy-3-methyl-benzoyl)-4-phenyl-5-oxa-2,9-diazaspiro[5.5]undecan-3-one as a viscous oil. 1H NMR (400 MHz, CDCl3) δ 7.48-7.43 (m, 2H), 7.39-7.29 (m, 3H), 7.23-7.17 (m, 2H), 6.81 (d, J=8.2 Hz, 1H), 5.11 (s, 1H), 4.56 (dt, J=12.1, 6.0 Hz, 1H), 3.63 (d, J=12.4 Hz, 1H), 3.59-3.19 (m, 5H), 3.09 (d, J=12.4 Hz, 1H), 2.92 (d, J=28.7 Hz, 1H), 2.22 (s, 1H), 2.23-2.16 (m, 3H), 1.59 (s, 3H), 1.35 (d, J=6.0 Hz, 6H), 1.14 (t, J=7.2 Hz, 3H). ESI-MS m/z calc. 450.3. Found 451.1 (M+1)+; Retention time: 1.76 minutes (3 min run).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 16 hours
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. custompurified by silica gel column chromatography

Sources & evidence

ORD record
ord-25904914f61047a0b9089f12a4692479
Source dataset
uspto-grants-2014_09
Patent number
US08828996B2

Reaction notes

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