Diisopropylethylamine → Ethyl 5-(3-hydroxyazetidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylate

HRID 1845182Notes

Reaction equation

HRID 1845182 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:19](O)=[O:20])[CH:9]=[C:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)[CH:11]=1)=[O:5])[CH3:2].Cl.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.Cl.[OH:46][CH:47]1[CH2:50][NH:49][CH2:48]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[OH:46][CH:47]1[CH2:50][N:49]([C:19]([C:8]2[CH:7]=[C:6]([C:4]([O:3][CH2:1][CH3:2])=[O:5])[CH:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=3)[CH:9]=2)=[O:20])[CH2:48]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27592903-Hydroxyazetidine hydrochlorideHCID 27960291-Hydroxybenzotriazole hydrateHCID 581879575-(Ethoxycarbonyl)-4'-methylbiphenyl-3-carboxylic acid

Product 1

HCID 58187978Ethyl 5-(3-hydroxyazetidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a mixture of 5-(ethoxycarbonyl)-4′-methylbiphenyl-3-carboxylic acid (2.0 g, 7.0 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.7 g, 14 mmol), 1-hydroxybenzotriazole hydrate (1.1 g, 7.0 mmol), and CH2Cl2 (50 mL) were added 3-hydroxyazetidine hydrochloride (1.2 g, 10 mmol) and N,N-diisopropylethylamine (3.7 mL, 21 mmol). The mixture was stirred at room temperature for 5 h, and then washed with brine and aq. Na2CO3 solution, dried (Na2SO4), and concentrated in vacuo. The residue was purified by silica gel column (0-10% MeOH/CH2Cl2) to afford a syrup. LC-MS: 340.4 [M+1]+; 1H NMR (400 MHz, CDCl3): 8.34 (t, 1H, J=1.6 Hz), 8.19 (t, 1H, J=1.6 Hz), 8.04 (t, 1H, J=1.6 Hz), 7.52 (d, 2H, J=8.4 Hz), 7.28 (d, 2H, J=8.4 Hz), 4.75 (bs, 1H), 4.50 (m, 2H), 4.41 (q, 2H, J=7.2 Hz), 4.25 (bs, 1H), 4.10 (bs, 1H), 2.82 (bs, 1H), 2.41 (s, 3H), 1.42 (t, 3H, J=7.2 Hz).

Workup

  1. washwashed with brine and aq. Na2CO3 solution
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel column (0-10% MeOH/CH2Cl2)
  5. customto afford a syrup

Sources & evidence

ORD record
ord-f77e4ac590d744ea9526d88932c83a77
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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