Cesium carbonate → [9-(6-Fluoro-pyridin-2-ylmethyl)-6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl]-carbamic acid benzyl ester

HRID 545543Notes

Reaction equation

C([O-])([O-])=O.[Cs+].[Cs+].[CH2:7]([O:14][C:15](=[O:35])[NH:16][CH:17]1[CH2:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([O:30][C:31]([F:34])([F:33])[F:32])[CH:26]=3)[NH:21][C:20]=2[CH2:19][CH2:18]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.Br[CH2:37][C:38]1[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[N:39]=1>CN(C=O)C.CCOC(C)=O>[CH2:7]([O:14][C:15](=[O:35])[NH:16][CH:17]1[CH2:29][C:28]2[C:27]3[C:22](=[CH:23][CH:24]=[C:25]([O:30][C:31]([F:34])([F:32])[F:33])[CH:26]=3)[N:21]([CH2:37][C:38]3[CH:43]=[CH:42][CH:41]=[C:40]([F:44])[N:39]=3)[C:20]=2[CH2:19][CH2:18]1)[C:8]1[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=1

Participants

Conditions

Temperature: 50 °C

Procedure

Add Cs2CO3 (6.44 g, 19.8 mmol) to a solution of (6-trifluoromethoxy-2,3,4,9-tetrahydro-1H-carbazol-3-yl)-carbamic acid benzyl ester (Preparation 43) (4.00 g, 9.88 mmol) and 2-bromomethyl-6-fluoropyridine (Preparation 44) (3.11 g, 13.8 mmol) in DMF (40 mL). Heat the resulting mixture to 50° C. for 18 h and then dilute with EtOAc (120 mL). Wash the organics with water (3×40 mL), dry (MgSO4), filter, and concentrate to give the crude product (5.40 g) as a brown oil. Purify the crude product on silica gel (120 g) eluting with 2545% EtOAc/hexanes to afford 2.85 g (56%) of the title compound as a tan oil. MS (ES): m/z 514 (M+1); HPLC (Method A): Rt=4.54 min (95%).

Workup

washWash the organics with water (3×40 mL)
dry with materialdry (MgSO4)
filtrationfilter
concentrationconcentrate
customto give the crude product (5.40 g) as a brown oil
customPurify the crude product on silica gel (120 g)
washeluting with 2545% EtOAc/hexanes

Sources & evidence

ORD record: ord-ea50097c052845c5b040c5e455d2e374
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07935722B2

Reaction notes

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