Dichloromethane → HCID 67251596, compound

HRID 2427278Notes

Reaction equation

HRID 2427278 reaction equation
[C:1]([O:5][C:6](=[O:22])[NH:7][CH:8]1[CH2:21][C:11]2[NH:12][C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])([CH3:3])[CH3:2].ClCCl.Br.Br[CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=1.[OH-].[Na+]>S([O-])(O)(=O)=O.C([N+](CCCC)(CCCC)CCCC)CCC.O>[C:1]([O:5][C:6](=[O:22])[NH:7][CH:8]1[CH2:21][C:11]2[N:12]([CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][N:30]=3)[C:13]3[CH:14]=[CH:15][C:16]([C:19]#[N:20])=[CH:17][C:18]=3[C:10]=2[CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 14798Sodium HydroxideHCID 27347202-(Bromomethyl)pyridine hydrobromideHCID 66933294tert-Butyl (7-cyano-1,2,3,4-tetrahydrocyclopenta[b]indol-2-yl)carbamate

Product 1

HCID 67251596HCID 67251596, compoundYield 85.8%

Reagents, catalysts & solvents 2

HCID 94433Tetrabutylammonium hydrogen sulfateCatalystHCID 962WaterSolvent

Procedure

Equip a 20 L bottom outlet flask with overhead agitation, thermocouple, and nitrogen inlet. Charge the flask with (±)-(7-cyano-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-yl)-carbamic acid tert-butyl ester (500 g, 1.68 moles) and dichloromethane (5 L). Begin agitation and add tetra n-butylammonium hydrogen sulfate (58.9 g, 0.168 mol) followed by 2-(bromomethyl)pyridine hydrobromide (510.4 g, 2.02 moles). Add deionized water (2 L) followed by a 50% NaOH solution (445.3 mL, 8.41 moles). Stir the resulting mixture vigorously overnight (about 21 h). Stop the agitation, allow the layers to separate, and discard the aqueous (upper) layer. Wash the organics with deionized water (3×4 L), dry over sodium sulfate, and concentrate in vacuo to about 500 mL. Purify the crude material over a silica gel plug (7 Kg Keiselgel 60) using 1:1 ethyl acetate/heptane as eluent. Concentrate the eluent in vacuo to afford 560 grams of the titled compound as an off-white solid (81.4%).

Workup

  1. customEquip a 20 L bottom outlet flask with overhead agitation
  2. customto separate
  3. washWash the organics with deionized water (3×4 L)
  4. dry with materialdry over sodium sulfate
  5. concentrationconcentrate in vacuo to about 500 mL
  6. customPurify the crude material over a silica gel plug (7 Kg Keiselgel 60)
  7. concentrationConcentrate the eluent in vacuo

Sources & evidence

ORD record
ord-b73747279ad64141aff696014c3b3ea9
Source dataset
uspto-grants-2011_06
Patent number
US07968587B2

Reaction notes

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