Diisopropylethylamine → 3-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acid

HRID 1014870

Reaction equation

HRID 1014870 reaction equation
C(O[C:6]([N:8]1[CH2:12][C@H:11]([OH:13])C[C@@H]1C(O)=O)=O)(C)(C)C.Br[C:18]1[CH:19]=[C:20]([CH:25]=[C:26]([C:28]([N:30]2[CH2:34][CH2:33][CH2:32][C@@H:31]2[CH2:35][O:36][CH3:37])=[O:29])[CH:27]=1)[C:21]([O:23]C)=[O:22].BrC1C=C(C=C(C(OC)=O)C=1)C(O)=O.CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.COC[C@H]1CCCN1>ClCCl>[CH3:37][O:36][CH2:35][C@H:31]1[CH2:32][CH2:33][CH2:34][N:30]1[C:28]([C:26]1[CH:25]=[C:20]([CH:19]=[C:18]([C:6]2[O:13][CH:11]=[CH:12][N:8]=2)[CH:27]=1)[C:21]([OH:23])=[O:22])=[O:29]

Participants

8

Reactant 6

HCID 81531DiisopropylethylamineHCID 671216(2R)-2-(Methoxymethyl)pyrrolidineHCID 688616N-Boc-cis-4-hydroxy-D-prolineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 225936413-Bromo-5-(methoxycarbonyl)benzoic acidHCID 67315972(R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate

Product 1

HCID 593468493-((R)-2-(methoxymethyl)pyrrolidine-1-carbonyl)-5-(oxazol-2-yl)benzoic acidYield 73%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

Step H (1): (R)-methyl 3-bromo-5-(2-(methoxymethyl)pyrrolidine-1-carbonyl)benzoate. To a solution of 3-bromo-5-(methoxycarbonyl)benzoic acid (1.8 g, 6.95 mmol) in dichloromethane (100 mL) and was added Hunig's base (2.7 g, 20.85 mmol) to make a clear solution and HATU (3.17 g, 8.34 mmol) was then added. After stirring for 30 min, the reaction mixture was added (R)-2-(methoxymethyl)pyrrolidine (800 mg, 6.95 mmol) and the reaction mixture was stirred at rt for 6 h. Dichloromethane (100 mL) was added and the mixture was washed with 1N NaOH, H2O and concentrated under vacuum. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient) to give 1.8 g of the title compound (73% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 1.77-2.08 (4H, m), 3.14-3.47 (5H, m), 3.63 (2H, brd s), 3.82 (3H, s), 4.41 (1H, brd s), 7.83 (1H, s), 8.07 (1H, s), 8.20 (1H, m).

Workup

  1. additionwas then added
  2. stirringthe reaction mixture was stirred at rt for 6 h
  3. washthe mixture was washed with 1N NaOH, H2O
  4. concentrationconcentrated under vacuum
  5. customThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% EtOAc/Hexane step gradient)

Sources & evidence

ORD record
ord-d2757070500040aebd3fc7a15d813b2b
Source dataset
uspto-grants-2011_07
Patent number
US07981913B2

Linked notes

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