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

HRID 1845213Notes

Reaction equation

HRID 1845213 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.[OH:45][C@@H:46]1[CH2:50][CH2:49][NH:48][CH2:47]1.C(N(CC)C(C)C)(C)C>C(Cl)Cl>[OH:45][C@@H:46]1[CH2:50][CH2:49][N:48]([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:13]=[CH:14][C:15]([CH3:18])=[CH:16][CH:17]=3)[CH:9]=2)=[O:20])[CH2:47]1

Participants

7

Reactant 5

HCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2759337(R)-3-PyrrolidinolHCID 27960291-Hydroxybenzotriazole hydrateHCID 581879575-(Ethoxycarbonyl)-4'-methylbiphenyl-3-carboxylic acid

Product 1

HCID 58188314(R)-Ethyl 5-(3-hydroxypyrrolidine-1-carbonyl)-4'-methylbiphenyl-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a mixture of 5-(ethoxycarbonyl)-4′-methylbiphenyl-3-carboxylic acid (1.50 g, 5.28 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (2.0 g, 10 mmol), 1-hydroxybenzotriazole hydrate (0.404 g, 2.64 mmol), and CH2Cl2 (30 mL) were added (R)-3-hydroxypyrrolidine (0.92 g, 10 mmol) and N,N-diisopropylethylamine (1.8 mL, 10 mmol). The mixture was stirred at room temperature overnight, and then diluted with CH2Cl2 (100 mL), washed with aq. NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo. The residue was purified by silica gel column (100% EtOAc) to afford a white foam. LC-MS: 354.2 [M+1]+; 1H NMR (400 MHz, CDCl3): 8.32 (s, 1H), 8.16 and 8.12 (bs, 1H), 7.92 (m, 1H), 7.53 (d, 2H, J=7.6 Hz), 7.28 (d, 2H, J=8.4 Hz), 4.63 and 4.49 (bs, 1H), 4.41 (q, 2H, J=7.2 Hz), 3.95-3.40 (m, 4H), 2.41 (s, 3H), 2.20-1.90 (m, 2H), 1.41 (t, 3H, J=7.2 Hz).

Workup

  1. washwashed with aq. NaHCO3, brine
  2. dry with materialdried (Na2SO4)
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by silica gel column (100% EtOAc)
  5. customto afford a white foam

Sources & evidence

ORD record
ord-cd806b11768c4545b032a1d0a02f310a
Source dataset
uspto-grants-2015_02
Patent number
US08946439B2

Reaction notes

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