Diisopropylethylamine → Ethyl 3-(4-(cyclobutyl(hydroxy)methyl)benzamido)propanoate

HRID 537482Notes

Reaction equation

HRID 537482 reaction equation
[CH:1]1([CH:5]([OH:15])[C:6]2[CH:14]=[CH:13][C:9]([C:10]([OH:12])=O)=[CH:8][CH:7]=2)[CH2:4][CH2:3][CH2:2]1.Cl.[NH2:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21].F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C>CN(C)C=O>[CH:1]1([CH:5]([OH:15])[C:6]2[CH:7]=[CH:8][C:9]([C:10]([NH:17][CH2:18][CH2:19][C:20]([O:22][CH2:23][CH3:24])=[O:21])=[O:12])=[CH:13][CH:14]=2)[CH2:2][CH2:3][CH2:4]1

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 458475beta-Alanine, ethyl ester, hydrochlorideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 681568354-(Cyclobutyl(hydroxy)methyl)benzoic acid

Product 1

HCID 68156469Ethyl 3-(4-(cyclobutyl(hydroxy)methyl)benzamido)propanoateYield 104.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

N,N-dimethylformamide (9.00 mL) was added to a vial containing 4-(cyclobutyl(hydroxy)methyl)benzoic acid (370 mg, 1.79 mmol), ethyl 3-aminopropanoate hydrochloride (551 mg, 3.59 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (1.36 g, 3.59 mmol). Diisopropylethylamine (1.56 mL, 8.97 mmol) was then added. The reaction was stirred for 1.5 h, and was then concentrated. Purification by column chromatography (0-50% ethyl acetate in heptane) afforded ethyl 3-(4-(cyclobutyl(hydroxy)methyl)benzamido)propanoate (570 mg, 100% yield) as a white solid. 1H NMR (400 MHz, CDCl3) δ7.73 (d, J=8.2 Hz, 2H), 7.38 (d, J=8.2 Hz, 2H), 4.63 (d, J=7.8 Hz, 1H), 4.17 (q, J=7.2 Hz, 2H), 3.72 (q, J=6.0 Hz, 2H), 2.64 (t, J=5.9 Hz, 2H), 2.61-2.54 (m, 1H), 2.08-1.95 (m, 2H), 1.88-1.75 (m, 4H), 1.27 (t, J=7.1 Hz, 3H). MS (M+1): 306.3.

Workup

  1. concentrationwas then concentrated
  2. customPurification by column chromatography (0-50% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-7382e4e5e8254ea3b1d58bb92c73cd4a
Source dataset
uspto-grants-2014_10
Patent number
US08859591B2

Reaction notes

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