Methyl chloroacetate → HCID 57812372, compound

HRID 912000Notes

Reaction equation

[Cl:1][C:2]1[C:7]([F:8])=[CH:6][CH:5]=[C:4]([Cl:9])[C:3]=1[C@H:10]([O:12][C:13]1[C:14]2[O:22][CH:21]=[C:20]([C:23]3[CH2:24][CH2:25][NH:26][CH2:27][CH:28]=3)[C:15]=2[CH:16]=[N:17][C:18]=1[NH2:19])[CH3:11].C(=O)([O-])[O-].[Cs+].[Cs+].C[O:36][C:37](=[O:40])[CH2:38]Cl>CN(C=O)C>[NH2:19][C:18]1[N:17]=[CH:16][C:15]2[C:20]([C:23]3[CH2:24][CH2:25][N:26]([CH2:38][C:37]([OH:40])=[O:36])[CH2:27][CH:28]=3)=[CH:21][O:22][C:14]=2[C:13]=1[O:12][C@@H:10]([C:3]1[C:4]([Cl:9])=[CH:5][CH:6]=[C:7]([F:8])[C:2]=1[Cl:1])[CH3:11]

Participants

Conditions

Temperature: 40 °C

Procedure

A mixture of 7-[(R)-1-(2,6-dichloro-3-fluorophenyl)ethoxy]-3-(1,2,3,6-tetrahydropyridin-4-yl)-furo[3,2-c]pyridine-6-ylamine (150.0 mg, 0.355 mmol), cesium carbonate (463 mg, 1.42 mmol) and DMF (4 mL) at rt was charged with chloroacetic acid methyl ester (37 μL, 0.43 mmol) and heated to 40° C. overnight. The solvent was removed in vacuo, and the material was dry-loaded onto silica gel for column chromatography, eluting with 2-5% MeOH/DCM. The fractions containing the pure ester were concentrated in vacuo and redissolved in EtOH (4 mL). The solution was charged with 2M aq. LiOH (0.9 mL) at rt, and stirred for 10 min. The solvents were removed in vacuo to afford the title compound as an orange solid. MS (ES+): m/z 497.97 (100) [MH+]. HPLC: tR=2.36 min (ZQ3, polar—5 min).

Workup

customThe solvent was removed in vacuo
washeluting with 2-5% MeOH/DCM
additionThe fractions containing the pure ester
concentrationwere concentrated in vacuo
dissolutionredissolved in EtOH (4 mL)
additionThe solution was charged with 2M aq. LiOH (0.9 mL) at rt
customThe solvents were removed in vacuo

Sources & evidence

ORD record: ord-6de62765543d4b7c866869187d57349c
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08022206B2

Reaction notes

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