Imidazole → 2-tert-butoxycarbonylamino-3-[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid methyl ester

HRID 1782682Notes

Reaction equation

HRID 1782682 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][CH2:9][N:10]2[CH2:13][C:14]2[CH:15]=[C:16]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26]O)=[CH:22][CH:21]=3)[CH:17]=[CH:18][CH:19]=2)=[CH:5][CH:4]=1.[CH3:30][O:31][C:32](=[O:44])[CH:33]([NH:36][C:37]([O:39][C:40]([CH3:43])([CH3:42])[CH3:41])=[O:38])[CH2:34][SH:35].N(C(N1CCCCC1)=O)=NC(N1CCCCC1)=O.N1C=CN=C1.CP(C)C>ClCCl.CCCCCCC>[CH3:30][O:31][C:32](=[O:44])[CH:33]([NH:36][C:37]([O:39][C:40]([CH3:41])([CH3:43])[CH3:42])=[O:38])[CH2:34][S:35][CH2:26][C:23]1[CH:24]=[CH:25][C:20]([C:16]2[CH:17]=[CH:18][CH:19]=[C:14]([CH2:13][N:10]3[C:11]4[C:6](=[CH:5][CH:4]=[C:3]([C:2]([F:29])([F:1])[F:28])[CH:12]=4)[CH2:7][CH2:8][CH2:9]3)[CH:15]=2)=[CH:21][CH:22]=1

Participants

8

Reactant 5

HCID 795ImidazoleHCID 68983TrimethylphosphineHCID 730421,1'-(Azodicarbonyl)dipiperidineHCID 4399784Methyl 2-(((tert-butoxy)carbonyl)amino)-3-sulfanylpropanoateHCID 11603644[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-yl]-methanol

Product 1

HCID 688198522-tert-butoxycarbonylamino-3-[3'-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid methyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8900HeptaneSolvent

Procedure

Under a nitrogen atmosphere, a solution of [3′-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-yl]-methanol (0.257 g, 0.65 mmol), 2-tert-butoxycarbonylamino-3-mercapto-propionic acid methyl ester (0.304 g, 1.29 mmol), 1,1′-(azodicarbonyl)dipiperidine (0.343 g, 1.36 mmol), and imidazole (0.92 g, 1.36 mmol) in dichloromethane (10 mL, 0.07 M) was treated with trimethylphosphine (1 M in toluene; 1.4 mL, 1.36 mmol) in a dropwise manner at room temperature. After stirring for 1 hour, an equal volume of heptane was added and the resulting precipitate was removed by filtration. The filtrate was concentrated and purified by flash chromatography (20% ethyl acetate in heptane) to give 2-tert-butoxycarbonylamino-3-[3′-(7-trifluoromethyl-3,4-dihydro-2H-quinolin-1-ylmethyl)-biphenyl-4-ylmethylsulfanyl]-propionic acid methyl ester as a white solid.

Workup

  1. customthe resulting precipitate was removed by filtration
  2. concentrationThe filtrate was concentrated
  3. custompurified by flash chromatography (20% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-167f9e071d6e41f2b5c42031809a40b8
Source dataset
uspto-grants-2009_03
Patent number
US07498356B2

Reaction notes

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