Carbamate → HCID 67475332, compound

HRID 1516336Notes

Reaction equation

HRID 1516336 reaction equation
C(=O)([O-])N.[F:5][C:6]1[CH:36]=[CH:35][C:9]([C:10]([NH:12][C@@H:13]2[C:19]3[CH:20]=[C:21]([N:24]4[CH2:29][CH2:28][N:27]([CH:30]5[CH2:33][O:32][CH2:31]5)[CH2:26][CH2:25]4)[CH:22]=[CH:23][C:18]=3[CH2:17][CH2:16][CH2:15][C@H:14]2[OH:34])=[O:11])=[CH:8][CH:7]=1.[CH3:37][NH:38][C:39](=O)[O-:40]>ClCCl.CO>[F:5][C:6]1[CH:7]=[CH:8][C:9]([C:10]([NH:12][C@H:13]2[C:19]3[CH:20]=[C:21]([N:24]4[CH2:29][CH2:28][N:27]([CH:30]5[CH2:33][O:32][CH2:31]5)[CH2:26][CH2:25]4)[CH:22]=[CH:23][C:18]=3[CH2:17][CH2:16][CH2:15][C@@H:14]2[O:34][C:39](=[O:40])[NH:38][CH3:37])=[O:11])=[CH:35][CH:36]=1

Participants

6

Reactant 3

HCID 276CarbamateHCID 21584661Npc184782HCID 131729847HCID 131729847, compound

Product 1

HCID 67475332HCID 67475332, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Prepare the racemic carbamate using racemic-trans-4-fluoro-N-[8-hydroxy-2-[4-(oxetan-3-yl)piperazin-1-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-9-yl]benzamide by essentially following the procedure for Example 1, above. LC-ES/MS m/z 497 [M+H]+. Dissolve racemic-trans-9-[(4-fluorobenzoyl)amino]-2-[4-(oxetan-3-yl)piperazin-1-yl]-6,7,8,9-tetrahydro-5H-benzo[7]annulen-8-yl]N-methylcarbamate (1.03 g) in dichloromethane (8 mL) and methanol (3 mL). Separate the enantiomers in 300 μL portions by SFC on a CHIRALPAK® AD-H column (2.1×25 cm, 5 μm). Mobile phase: 30% isopropanol with 0.2% isopropylamine/carbon dioxide. Flow rate: 70 mL/min. Detection: 225 nm. Obtain the title compound as isomer 1 (333 mg, 99% ee) and the 8R, 9R enantiomer as isomer 2 (359 mg, 97.5% ee). Determine enantiomeric excess by SFC on a CHIRALPAK® AD-H (4.6×150 mm, 5 μm) column using 30% isopropanol with 0.2% isopropylamine/carbon dioxide. Flow rate: 5 mL/min. Detection: 225 nm. Isomer 1 (title compound) TR=1.76 min. Isomer 2 TR=2.30 min.

Workup

  1. customSeparate the enantiomers in 300 μL portions by SFC on a CHIRALPAK® AD-H column (2.1×25 cm, 5 μm)

Sources & evidence

ORD record
ord-00c0d0da3abc4d67b554cd2b23b304cf
Source dataset
uspto-grants-2012_07
Patent number
US08227468B2

Reaction notes

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