4-tert-Butylbenzoyl chloride → (S)-methyl 4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoate

HRID 1622982Notes

Reaction equation

HRID 1622982 reaction equation
[NH2:1][C@H:2]([C:14]([O:16][CH3:17])=[O:15])[CH2:3][C:4]1[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=1.CCN(C(C)C)C(C)C.[C:27]([C:31]1[CH:39]=[CH:38][C:34]([C:35](Cl)=[O:36])=[CH:33][CH:32]=1)([CH3:30])([CH3:29])[CH3:28]>C(Cl)Cl>[C:27]([C:31]1[CH:32]=[CH:33][C:34]([C:35]([NH:1][C@H:2]([C:14]([O:16][CH3:17])=[O:15])[CH2:3][C:4]2[CH:13]=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[CH:6][CH:5]=2)=[O:36])=[CH:38][CH:39]=1)([CH3:30])([CH3:28])[CH3:29]

Participants

5

Reactant 3

HCID 743724-tert-Butylbenzoyl chlorideHCID 81531DiisopropylethylamineHCID 86689653(S)-methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate

Product 1

HCID 86689654(S)-methyl 4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoateYield 45%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Prepared using General Procedure 3: To the solution of (S)-methyl 4-(2-amino-3-methoxy-3-oxopropyl)benzoate (425.0 mg, 1.79 mmol) in DCM (10 mL) and DIEA (463.0 mg, 3.58 mmol) was added 4-(tert-butyl)benzoyl chloride (556.6 mg, 2.83 mmol) at RT. The reaction was stirred for 2 h and the reaction was partitioned between DCM and saturated aqueous NaHCO3. The organic layer was dried over MgSO4 and concentrated. The crude product was purified by chromatography (EA/hexanes) to afford 317 mg (45%) of (S)-methyl 4-(2-(4-(tert-butyl)benzamido)-3-methoxy-3-oxopropyl)benzoate. LCMS-ESI (m/z) calculated for C23H27NO5: 397.2; found 398.1 [M+H]+, tR=2.31 min (Method 1). 1H NMR (400 MHz, CDCl3) δ 7.97-7.75 (m, 2H), 7.67-7.51 (m, 2H), 7.46-7.26 (m, 2H), 7.14 (d, J=8.3 Hz, 2H), 6.60 (d, J=7.4 Hz, 1H), 5.03 (dt, J=7.4, 5.7 Hz, 1H), 3.82 (s, 3H), 3.68 (s, 3H), 3.28 (dd, J=13.7, 5.8 Hz, 1H), 3.18 (dd, J=13.7, 5.5 Hz, 1H), 1.24 (s, 9H).

Workup

  1. customPrepared
  2. customthe reaction was partitioned between DCM and saturated aqueous NaHCO3
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated
  5. customThe crude product was purified by chromatography (EA/hexanes)

Sources & evidence

ORD record
ord-9f8d6f5131ea422dbee4dfa0efafd790
Source dataset
uspto-grants-2014_07
Patent number
US08778923B2

Reaction notes

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