tert-Butyl bromoacetate → Tert-butyl[1-(2-methoxyethyl)-2-oxo-6-phenylazepan-3-yl]acetate

HRID 1365993Notes

Reaction equation

HRID 1365993 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][O:10][CH2:11][CH2:12][N:13]1[CH2:19][CH:18]([C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)[CH2:17][CH2:16][CH2:15][C:14]1=[O:26].[C:27]([O:31][C:32](=[O:35])[CH2:33]Br)([CH3:30])([CH3:29])[CH3:28]>O1CCCC1>[C:27]([O:31][C:32](=[O:35])[CH2:33][CH:15]1[CH2:16][CH2:17][CH:18]([C:20]2[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=2)[CH2:19][N:13]([CH2:12][CH2:11][O:10][CH3:9])[C:14]1=[O:26])([CH3:30])([CH3:29])[CH3:28]

Participants

5

Reactant 3

HCID 79177tert-Butyl bromoacetateHCID 2724682Lithium diisopropylamideHCID 222931831-(2-Methoxyethyl)-6-phenylazepan-2-one

Product 1

HCID 22293188Tert-butyl[1-(2-methoxyethyl)-2-oxo-6-phenylazepan-3-yl]acetate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium diisopropylamide (1.8 M in heptane/tetrahydrofuran/ethylbenzene; 0.58 g, 5.41 mmol) was added to a solution of 1-(2-methoxyethyl)-6-phenylazepan-2-one (1.03 g, 4.16 mmol) in tetrahydrofuran (40 mL) at −78° C. After 2 h, tert-butylbromoacetate was added. After an additional 1.5 h, the reaction was quenched with methanol and allowed to warm to ambient temperature and concentrated. Purification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid) gave 450 mg (cis isomer) and 350 mg (trans isomer) of the title compound. MS 362 (M+1). cis isomer: 1H NMR (500 MHz, CDCl3) δ 7.29 (t, J=7.6 Hz, 2H), 7.26 (m, 1H), 7.22-7.20 (m, 2H), 4.04 (br d, J=15.2 Hz, 1H), 3.84 (dt, J=13.9, 4.9 Hz, 1H), 3.51 (dd, J=15.4, 3.9 Hz, 1H), 3.40-3.35 (m, 1H), 3.30-3.21 (m, 2H), 3.24 (s, 3H), 3.02-3.00 (m, 1H), 2.84 (dd, J=16.4, 7.6 Hz, 1H), 2.68-2.66 (m, 1H), 2.33 (dd, J=16.4, 6.8 Hz, 1H), 2.11-2.07 (m, 1H), 2.05-1.95 (m, 1H), 1.80-1.76 (m, 2H), 1.46 (s, 9H). trans isomer: 1H NMR (500 MHz, CDCl3) δ 7.32 (t, J=7.3 Hz, 2H), 7.24-7.21 (m, 1H), 7.18 (d, J=7.1 Hz, 2H), 3.96 (dd, J=14.9, 10.0 Hz, 1H), 3.82-3.77 (m, 1H), 3.56-3.46 (m, 2H), 3.43-3.38 (m, 1H), 3.34 (s, 3H), 3.30 (d, J=15.1 Hz, 1H), 3.20-3.15 (m, 1H), 2.85 (dd, J=16.6, 7.8 Hz, 1H), 2.78 (br t, 1H), 2.26 (dd, J=16.6, 6.6 Hz, 1H), 2.10 (br d, J=22.7, 9.3 Hz, 1H), 1.77-1.73 (m, 1H), 1.62-1.59 (m, 1H), 1.46 (s, 9H).

Workup

  1. waitAfter an additional 1.5 h
  2. customthe reaction was quenched with methanol
  3. concentrationconcentrated
  4. customPurification by reverse phase HPLC (C-18, 95% water/acetonitrile→5% water/acetonitrile with 0.1% trifluoroacetic acid)

Sources & evidence

ORD record
ord-1742f1bc3e0a4b66919b11a93969e778
Source dataset
uspto-grants-2011_02
Patent number
US07893052B2

Reaction notes

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