Triphenylphosphine → 6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

HRID 2374447

Reaction equation

HRID 2374447 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18][OH:19])[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:20][C:21]1[CH:26]=[CH:25][C:24](O)=[CH:23][C:22]=1[C:28]([F:31])([F:30])[F:29].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13]([CH2:18][O:19][C:24]3[CH:25]=[CH:26][C:21]([Cl:20])=[C:22]([C:28]([F:31])([F:30])[F:29])[CH:23]=3)[CH:14]=2)[CH2:9]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 805204-Chloro-3-(trifluoromethyl)phenolHCID 59132278Tert-butyl 6-(hydroxymethyl)-1,2,3,4-tetrahydroisoquinoline-2-carboxylate

Product 1

HCID 691462886-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl esterYield 49%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 6-hydroxymethyl-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester (85 mg, 0.323 mmol) in CH2Cl2 (1.5 mL) is added a solution of 4-chloro-3-trifluoromethyl-phenol (76 mg, 1.23 eq.) in CH2Cl2 (0.5 mL), PPh3 (127 mg, 1.5 eq.), and 1,1′-(azodicarbonyl)-dipiperidine (122 mg, 1.5 eq.). The mixture is stirred at room temperature overnight. All the solvent is removed under reduced pressure and the mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient) to give 70 mg of 6-(4-chloro-3-trifluoromethyl-phenoxymethyl)-3,4-dihydro-1H-isoquinoline-2-carboxylic acid tert-butyl ester

Workup

  1. customAll the solvent is removed under reduced pressure
  2. customthe mixture is purified by column chromatography (silica gel, EtOAc/Hexane, gradient)

Sources & evidence

ORD record
ord-bafc492e89c64c68b666ffba008967f7
Source dataset
uspto-grants-2008_12
Patent number
US07462629B2

Linked notes

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