Isopropyl chloroformate → propan-2-yl N-[(2S)-7-bromo-1H,2H,3H,4H-cyclopenta[b]indol-2-yl]carbamate

HRID 1928578Notes

Reaction equation

HRID 1928578 reaction equation
O[C@H](CC1C=CC=CC=1)C(O)=O.[Br:13][C:14]1[CH:22]=[CH:21][C:20]2[NH:19][C:18]3[CH2:23][C@@H:24]([NH2:26])[CH2:25][C:17]=3[C:16]=2[CH:15]=1.C(N(C(C)C)CC)(C)C.Cl[C:37]([O:39][CH:40]([CH3:42])[CH3:41])=[O:38]>C1(C)C=CC=CC=1>[CH:40]([O:39][C:37](=[O:38])[NH:26][C@@H:24]1[CH2:23][C:18]2[NH:19][C:20]3[CH:21]=[CH:22][C:14]([Br:13])=[CH:15][C:16]=3[C:17]=2[CH2:25]1)([CH3:42])[CH3:41]

Participants

5

Reactant 3

HCID 7917Isopropyl chloroformateHCID 81531DiisopropylethylamineHCID 131729738(S)-7-Bromo-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-ylamine(R)-2-hydroxy-3-phenylpropionic acid salt

Product 1

HCID 45588342propan-2-yl N-[(2S)-7-bromo-1H,2H,3H,4H-cyclopenta[b]indol-2-yl]carbamateYield 91.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Conditions

Temperature
0 °C

Procedure

(S)-7-Bromo-1,2,3,4-tetrahydro-cyclopenta[b]indol-2-ylamine(R)-2-hydroxy-3-phenylpropionic acid salt (60.00 g, 143.78 mmol) and diisopropylethylamine (50 mL, 296.12 mmol) are combined in toluene (165 mL). The reaction vessel is purged with nitrogen three times. The mixture is cooled to 0° C. with stirring and is held at that temperature for 30 min. A solution of isopropyl chloroformate (20.00 g, 163.20 mmol) in toluene (165 mL) is added at 0-5° C. over 10 min. The mixture is stirred at 5° C. for 10 min. HPLC shows 98.6% complete. The reaction is quenched with water (1 L) and ethyl acetate (480 mL). The mixture is filtered and the solid is washed with ethyl acetate (2×240 mL). The combined organic layer is washed with brine twice, dried (MgSO4), and filtered. The organic solvent is reduced to 50 mL. The mixture is cooled to 25° C. and tert-butyl methyl ether (50 mL) and ethyl acetate (50 mL) are added. An off-white solid is precipitated. The solid is filtered and washed with heptanes (100 mL). The solid is dried under vacuum at 50° C. for 4 h to give 44.4 g (90.3%) of a light brown solid.

Workup

  1. customThe reaction vessel is purged with nitrogen three times
  2. stirringThe mixture is stirred at 5° C. for 10 min
  3. customThe reaction is quenched with water (1 L) and ethyl acetate (480 mL)
  4. filtrationThe mixture is filtered
  5. washthe solid is washed with ethyl acetate (2×240 mL)
  6. washThe combined organic layer is washed with brine twice
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. temperatureThe mixture is cooled to 25° C.
  10. additiontert-butyl methyl ether (50 mL) and ethyl acetate (50 mL) are added
  11. customAn off-white solid is precipitated
  12. filtrationThe solid is filtered
  13. washwashed with heptanes (100 mL)
  14. customThe solid is dried under vacuum at 50° C. for 4 h

Sources & evidence

ORD record
ord-55d21e32c0384e69829652a7f36e0676
Source dataset
uspto-grants-2012_05
Patent number
US08183388B2

Reaction notes

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