Water → 1h-Pyrrolo[2,3-c]pyridine-5-carboxylic acid,1-[(2,4-difluorophenyl)methyl]-3-[(2-methoxyethoxy)methyl]-

HRID 2377119Notes

Reaction equation

[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([O:16]C)=[O:15])[CH:13]=[C:8]2[C:7]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23])=[CH:6]1.O.[OH-].[Li+].O>CO>[F:1][C:2]1[CH:27]=[C:26]([F:28])[CH:25]=[CH:24][C:3]=1[CH2:4][N:5]1[C:9]2=[CH:10][N:11]=[C:12]([C:14]([OH:16])=[O:15])[CH:13]=[C:8]2[C:7]([CH2:18][O:19][CH2:20][CH2:21][O:22][CH3:23])=[CH:6]1

Participants

Conditions

Temperature: 40 °C

Procedure

To a solution of methyl 1-(2,4-difluorobenzyl)-3-[(2-methoxyethoxy)methyl]-1H-pyrrolo[2,3-c]pyridine-5-carboxylate (2000 mg 5.123 mmol) in methanol (10 mL) was added lithium hydroxide monohydrate (430 mg 10.246 mmol, 2 eq.) and water (10 mL) and the clear solution was warmed to 40° C. for 3 hours. THF was removed under vacuum and 1 M HCl added (10.3 mL 10.3 mmol, 2 eq.). The crude product was extracted into EtOAc (3×30 mL), then DCM:MeOH 100:5 (3×30 mL). The organics were dried (Na2SO4), volatiles were removed in vacuo to give the title product as a cream colored powder 1563 mg (82%). LC-MS (Eclipse XDB-C8, 0.8 mL/min, gradient 80:20 to 5:95H2O (+0.1% HOAc):CH3CN—3 minutes, ESI, +mode): RT—0.91 min, m/e=377.2 (M+H+, base). 1H-NMR (300 MHz, DMSO): δ=3.42 (s, 3H), 3.46 (m, 2H), 3.60 (m, 2H), 4.69 (s, 2H), 5.66 (s, 2H), 7.07 (m, 1H), 7.36 (m, 2H), 7.82 (s, 1H), 8.36 (s, 1H), 8.98 (s, 1H).

Workup

customTHF was removed under vacuum and 1 M HCl
additionadded (10.3 mL 10.3 mmol, 2 eq.)
extractionThe crude product was extracted into EtOAc (3×30 mL)
dry with materialThe organics were dried (Na2SO4), volatiles
customwere removed in vacuo

Sources & evidence

ORD record: ord-503ef0a94e414a89b75ba3735d15e84e
Source dataset: uspto-grants-2008_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07468375B2

Reaction notes

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