1-Hydroxybenzotriazole → (2R)-1-[3-methoxy-5-(trifluoromethyl)-benzoyl]-2-[4-chloro-3-(tert-butyldimethylsilyloxy)benzyl]-4-benzylpiperazine

HRID 1374998Notes

Reaction equation

HRID 1374998 reaction equation
Cl.CN(C)CCCN=C=NCC.[CH2:13]([N:20]1[CH2:25][CH2:24][NH:23][C@H:22]([CH2:26][C:27]2[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH:28]=2)[CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[CH3:42][O:43][C:44]1[CH:45]=[C:46]([CH:50]=[C:51]([C:53]([F:56])([F:55])[F:54])[CH:52]=1)[C:47](O)=[O:48].ON1C2C=CC=CC=2N=N1.C(=O)([O-])O.[Na+]>ClCCl.O>[CH3:42][O:43][C:44]1[CH:45]=[C:46]([CH:50]=[C:51]([C:53]([F:54])([F:55])[F:56])[CH:52]=1)[C:47]([N:23]1[CH2:24][CH2:25][N:20]([CH2:13][C:14]2[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=2)[CH2:21][C@H:22]1[CH2:26][C:27]1[CH:32]=[CH:31][C:30]([Cl:33])=[C:29]([O:34][Si:35]([C:38]([CH3:41])([CH3:40])[CH3:39])([CH3:37])[CH3:36])[CH:28]=1)=[O:48]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 215444673-Methoxy-5-(trifluoromethyl)benzoic acidHCID 54436042(2R)-4-benzyl-2-[4-chloro-3-(tert-butyldimethylsilyloxy)benzyl]piperazine

Product 1

HCID 57092342(2R)-1-[3-methoxy-5-(trifluoromethyl)-benzoyl]-2-[4-chloro-3-(tert-butyldimethylsilyloxy)benzyl]-4-benzylpiperazineYield 77.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

1-[3-(Dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (1.93 g) was added to a mixture of (2R)-4-benzyl-2-[4-chloro-3-(tert-butyldimethylsilyloxy)benzyl]-piperazine (2.90 g) and 3-methoxy-5-(trifluoromethyl)benzoic acid (1.48 g), 1-hydroxybenzotriazole (1.14 g) in dichloromethane (18 ml) at room temperature. After being stirred for 6 hours at the same temperature, the reaction mixture was poured into a mixed solvent of water (25 ml) and dichloromethane (15 ml). The aqueous layer was adjusted to pH 9 with aqueous sodium hydrogen carbonate solution. The organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by column chromatography on silica gel (52 g) using a mixed solvent of hexane and ethyl acetate (2:1). The fractions containing the objective compound was collected and evaporated under reduced pressure to give a syrup of (2R)-1-[3-methoxy-5-(trifluoromethyl)-benzoyl]-2-[4-chloro-3-(tert-butyldimethylsilyloxy)benzyl]-4-benzylpiperazine (3.3 g).

Workup

  1. customThe organic layer was separated
  2. washwashed with brine
  3. dry with materialdried over sodium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe resulting residue was purified by column chromatography on silica gel (52 g)
  6. additionThe fractions containing the objective compound
  7. customwas collected
  8. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-5d9bd598391b4715a86c035ecbc1d9f1
Source dataset
uspto-grants-2007_01
Patent number
US07166598B2

Reaction notes

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