Hydrochloric Acid → 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid

HRID 926360Notes

Reaction equation

C([O:3][C:4]([C:6]1[CH:7]=[C:8]([C:15]([N:17]2[CH2:21][CH2:20][CH2:19][C@@H:18]2[CH3:22])=[O:16])[N:9]2[CH2:14][CH2:13][O:12][CH2:11][C:10]=12)=[O:5])C.O.[OH-].[K+].Cl>CO>[CH3:22][C@H:18]1[CH2:19][CH2:20][CH2:21][N:17]1[C:15]([C:8]1[N:9]2[C:10]([CH2:11][O:12][CH2:13][CH2:14]2)=[C:6]([C:4]([OH:5])=[O:3])[CH:7]=1)=[O:16]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid ethyl ester (Comp. No. 6c) (762 mg, 2.49 mmol) in methanol (10 ml) was added water (4 ml) and 2 N aqueous potassium hydroxide (6 ml, 12 mmol). The mixture was stirred for 3 h at 80° C., then cooled down to 25° C. and acidified with excess 10 M aqueous hydrochloric acid. After extraction (3 times with dichloromethane), the combined organic layers were dried over sodium sulfate and the solvents evaporated to give 595 mg (86%) 6-((S)-2-methyl-pyrrolidine-1-carbonyl)-3,4-dihydro-1H-pyrrolo[2,1-c][1,4]oxazine-8-carboxylic acid as a white solid. LC/MS (method 2): Rt=0.98 min; m/z=279.06 (M+H+).

Workup

temperaturecooled down to 25° C.
extractionAfter extraction (3 times with dichloromethane)
dry with materialthe combined organic layers were dried over sodium sulfate
customthe solvents evaporated

Sources & evidence

ORD record: ord-ac2a432110e34a39a265aefb7a246219
Source dataset: uspto-grants-2016_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09284333B2

Reaction notes

Loading…