4-(Chloromethyl)benzoyl chloride → N-[3-[[4-(Chloromethyl)benzoyl]amino][1,1'-biphenyl]-4-yl]carbamic Acid tert-Butyl Ester

HRID 1013529Notes

Reaction equation

HRID 1013529 reaction equation
[Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][CH:4]=1.[NH2:12][C:13]1[CH:14]=[C:15]([C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:16]=[CH:17][C:18]=1[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23].CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+]>C1COCC1>[Cl:1][CH2:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:12][C:13]2[CH:14]=[C:15]([C:27]3[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=3)[CH:16]=[CH:17][C:18]=2[NH:19][C:20](=[O:26])[O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:8])=[CH:5][CH:4]=1

Participants

6

Reactant 4

HCID 701364-(Chloromethyl)benzoyl chlorideHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 57717454N-(3-Amino[1,1'-biphenyl]-4-yl)-carbamic Acid tert-Butyl Ester

Product 1

HCID 57925998N-[3-[[4-(Chloromethyl)benzoyl]amino][1,1'-biphenyl]-4-yl]carbamic Acid tert-Butyl Ester

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

4-(chloromethyl)benzoyl chloride (12 g, 63.5 mmol) was dissolved in THF (120 mL) and a solution of 1,1-dimethylethyl (3-aminobiphenyl-4-yl)carbamate (19.86 g, 69.8 mmol) and DIPEA (12.2 mL, 69.8 mmol) in THF (300 mL) was added dropwise at room temperature. After stirring for 1 hour, saturated NaHCO3 was added and the products extracted into EtOAc (×2). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was triturated in Et2O to give 1,1-dimethylethyl [3-({[4-(chloromethyl)phenyl]carbonyl}amino)biphenyl-4-yl]carbamate as a white solid. 1H NMR (d6-DMSO, 600 MHz) δ 9.92 (s, 1H), 8.75 (s, 1H), 7.97 (d, J=8.4 Hz, 2H), 7.83 (s, 1H), 7.63 (m, 3H), 7.59 (d, J=8.4 Hz, 2H), 7.50 (dd, J=8.4 and 1.8 Hz, 1H), 7.44 (t, J=7.2 Hz, 2H), 7.33 (t, J=7.2 Hz, 1H), 4.84 (s, 2H), 1.44 (s, 9H).

Workup

  1. extractionthe products extracted into EtOAc (×2)
  2. dry with materialThe combined organic extracts were dried over MgSO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was triturated in Et2O

Sources & evidence

ORD record
ord-14b2a8f15465417f80837834641bd3df
Source dataset
uspto-grants-2011_07
Patent number
US07981874B2

Reaction notes

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