Sodium Hydroxide → 1-[2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl]-cyclopropanecarboxylic acid tert-butyl ester

HRID 501348Notes

Reaction equation

HRID 501348 reaction equation
[F:1][C:2]([F:19])([F:18])[C:3]1[CH:4]=[CH:5][C:6]2[C:10]([N:11]3[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]3)=[CH:9][S:8][C:7]=2[CH:17]=1.[C:20]([O:24][C:25]([C:27]1([CH2:30][CH:31]=O)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21].C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].[OH-].[Na+]>ClCCl>[C:20]([O:24][C:25]([C:27]1([CH2:30][CH2:31][N:14]2[CH2:13][CH2:12][N:11]([C:10]3[C:6]4[CH:5]=[CH:4][C:3]([C:2]([F:18])([F:1])[F:19])=[CH:17][C:7]=4[S:8][CH:9]=3)[CH2:16][CH2:15]2)[CH2:29][CH2:28]1)=[O:26])([CH3:23])([CH3:22])[CH3:21]

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 5049666Sodium triacetoxyborohydrideHCID 112891551-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazineHCID 58817571Tert-Butyl 1-(2-oxoethyl)cyclopropanecarboxylate

Product 1

HCID 588176151-[2-[4-(6-Trifluoromethyl-benzo[b]thiophen-3-yl)-piperazin-1-yl]-ethyl]-cyclopropanecarboxylic acid tert-butyl esterYield 91.2%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 4.2 g (14.7 mmol) of 1-(6-trifluoromethyl-benzo[b]thiophen-3-yl)-piperazine in 100 mL of dichloromethane under nitrogen was added 3.5 g (19.1 mmol) of 1-(2-Oxo-ethyl)-cyclopropanecarboxylic acid tert-butyl ester. After stirring 10 minutes at room temperature 6.5 g (30.7 mmol) of sodium triacetoxyborohydride was added portion-wise. After 30 minutes 100 mL of 0.5 N aqueous sodium hydroxide was added and the reaction was stirred for 15 minutes. The organic layer was separated, dried and concentrated to deliver a paste. This was taken up in methanolic hydrogen chloride. The salt thus obtained was recrystallized from ethyl acetate/methanol to deliver 6.6 g (13.4 mmol) of the desired product as a white powder mp=187-9° C.

Workup

  1. additionwas added portion-wise
  2. customThe organic layer was separated
  3. customdried
  4. concentrationconcentrated
  5. customThe salt thus obtained
  6. customwas recrystallized from ethyl acetate/methanol

Sources & evidence

ORD record
ord-37dd843dc371497e923b2aafdc91a92c
Source dataset
uspto-grants-2010_08
Patent number
US07772252B2

Reaction notes

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