Diisopropylethylamine → tert-Butyl ((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)carbamate

HRID 969560Notes

Reaction equation

HRID 969560 reaction equation
[F:1][C:2]([F:14])([F:13])[C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][NH:9][CH2:10]2)=[CH:5][CH:4]=1.[C:15]([O:19][C:20]([NH:22][C@@H:23]1[CH2:27][CH2:26][C@:25]([CH:31]([CH3:33])[CH3:32])([C:28](O)=[O:29])[CH2:24]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[CH:31]([C@:25]1([C:28]([N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][C:3]([C:2]([F:1])([F:13])[F:14])=[CH:4][CH:5]=3)[CH2:10]2)=[O:29])[CH2:26][CH2:27][C@@H:23]([NH:22][C:20](=[O:21])[O:19][C:15]([CH3:17])([CH3:16])[CH3:18])[CH2:24]1)([CH3:33])[CH3:32]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 103755517-(Trifluoromethyl)-1,2,3,4-tetrahydroisoquinolineHCID 60122293(1S,3R)-3-((Tert-butoxycarbonyl)amino)-1-isopropylcyclopentanecarboxylic acid

Product 1

HCID 58784552tert-Butyl ((1R,3S)-3-Isopropyl-3-{[7-(trifluoromethyl)-3,4-dihydroisoquinolin-2(1H)-yl]carbonyl}cyclopentyl)carbamateYield 55%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 7-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline (1.7 g, 8.45 mmol) of Step B-4, (1S,3R)-3-[(tert-butoxycarbonyl)amino]-1-isopropylcyclopentanecarboxylic acid (2.75 g, 10.14 mmol) of Step A-4,4-dimethylaminopyridine (0.70 g, 5.73 mmol), and N,N-diisopropylethylamine (7.0 mL, 40.2 mmol) in methylene chloride (30.0 mL) was added bromotris(pyrrolydino)phophonium hexafluorophosphate (5.119 g, 10.98 mmol). After being stirred for 36 h at room temperature, the solution was concentrated in vacuo. The residue was purified by column chromatography on silica eluting with 20% ethyl acetate/hexanes to give 2.1 g (55%) of desired product. MS calculated for C24H33F3N2O3: (M+H)+455; found 355 (M−Boc+H)+.

Workup

  1. concentrationthe solution was concentrated in vacuo
  2. customThe residue was purified by column chromatography on silica eluting with 20% ethyl acetate/hexanes

Sources & evidence

ORD record
ord-e3aa99943cdb43b39d78bcc420f93dd9
Source dataset
uspto-grants-2007_12
Patent number
US07307086B2

Reaction notes

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