Boron tribromide → [(S)-7-cyano-4-(3-fluoro-2-hydroxybenzyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-y]-carbamic acid isopropyl ester

HRID 449844Notes

Reaction equation

HRID 449844 reaction equation
[C:1]([C:3]1[CH:11]=[CH:10][C:9]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[O:20]C)[C:7]3[CH2:22][C@@H:23]([NH:25][C:26](=[O:31])[O:27][CH:28]([CH3:30])[CH3:29])[CH2:24][C:6]=3[C:5]=2[CH:4]=1)#[N:2].B(Br)(Br)Br>ClCCl>[CH:28]([O:27][C:26](=[O:31])[NH:25][C@@H:23]1[CH2:22][C:7]2[N:8]([CH2:12][C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([F:19])[C:14]=3[OH:20])[C:9]3[CH:10]=[CH:11][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[C:6]=2[CH2:24]1)([CH3:30])[CH3:29]

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 66933184(S)-isopropyl 7-cyano-4-(3-fluoro-2-methoxybenzyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamate

Product 1

HCID 44511591[(S)-7-cyano-4-(3-fluoro-2-hydroxybenzyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-y]-carbamic acid isopropyl esterYield 64.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

To a solution of (S)-isopropyl 7-cyano-4-(3-fluoro-2-methoxybenzyl)-1,2,3,4-tetrahydrocyclopenta[b]indol-2-ylcarbamate (1.88 g, 4.46 mmol) in dichloromethane (50 mL) is added 1 M boron tribromide in dichloromethane (13.4 mL, 13 4 mmol) at 0° C. and stirred overnight. The reaction is quenched with slightly wet acetonitrile. The volatiles are removed under reduced pressure and the residue is dried under high vacuum. It is then purified by column chromatography with 5% ethyl acetate in chloroform to obtain a yellow solid. The solid is suspended in a minimum amount of dichloromethane and allowed to sit at room temperature. White solids crash out. They are filtered and briefly rinsed with dichloromethane. The mother liquor is concentrated and the procedure is repeated with the residue three times. The white solids are combined to afford the title compound (1.17 g, 64%). LC-ES m/z 408.2 [M+H]+, TR=4.08 min.

Workup

  1. customThe reaction is quenched with slightly wet acetonitrile
  2. customThe volatiles are removed under reduced pressure
  3. customthe residue is dried under high vacuum
  4. customIt is then purified by column chromatography with 5% ethyl acetate in chloroform
  5. customto obtain a yellow solid
  6. customto sit at room temperature
  7. filtrationThey are filtered
  8. washbriefly rinsed with dichloromethane
  9. concentrationThe mother liquor is concentrated

Sources & evidence

ORD record
ord-6611873b86a14e038c27291ff46d5e7f
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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