Morpholine → HCID 68283902, compound

HRID 1527386Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH2:12][C@:11]([OH:19])([CH2:13]OS(C)(=O)=O)[CH2:10][C@H:9]1[C:20](=[O:31])[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[F:30])=[O:7])([CH3:4])([CH3:3])[CH3:2].[NH:32]1[CH2:37][CH2:36][O:35][CH2:34][CH2:33]1>CN(C=O)C.CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@:11]([OH:19])([CH2:13][N:32]2[CH2:37][CH2:36][O:35][CH2:34][CH2:33]2)[CH2:10][C@H:9]1[C:20](=[O:31])[NH:21][CH2:22][C:23]1[CH:28]=[CH:27][CH:26]=[C:25]([Cl:29])[C:24]=1[F:30])=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

Conditions

Temperature: 80 °C

Procedure

To a solution of (2S,4S)-2-(3-chloro-2-fluoro-benzylcarbamoyl)-4-hydroxy-4-methanesulfonyloxy methyl-pyrrolidine-1-carboxylic acid tert-butyl ester (200 mg, 0.416 mmol) (prepared as described Scheme B13) in DMF (10 mL) was added morpholine (181 mL, 2.079 mmol) and the solution was stirred for 16 h at 80° C. The reaction mixture was diluted with EtOAc, washed with a saturated aqueous solution of NaHCO3 (3 times). The organic layers were dried (Na2SO4), filtered and concentrated. The crude material was purified by flash column chromatography on silica gel (CH2Cl2/MeOH 8:2) to give the desired material. MS (LC/MS): 472.1/474.1 [M+H]+, 470.0/472.1 [M−H]−; tR (HPLC conditions f): 1.58 min; 19F NMR (100 MHz, DMSO-d6) δ (ppm): −120.

Workup

washwashed with a saturated aqueous solution of NaHCO3 (3 times)
dry with materialThe organic layers were dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by flash column chromatography on silica gel (CH2Cl2/MeOH 8:2)

Sources & evidence

ORD record: ord-ca7e41534cf54315b503496237a964c0
Source dataset: uspto-grants-2015_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09085555B2

Reaction notes

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