Triphenylphosphine → ethyl [(1S)-5-(3-{[6-chloro-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetate

HRID 2235934Notes

Reaction equation

HRID 2235934 reaction equation
[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][OH:12])[C:5]([C:13]([F:16])([F:15])[F:14])=[CH:4][CH:3]=1.[CH2:17]([O:19][C:20](=[O:32])[CH2:21][C@H:22]1[C:30]2[C:25](=[CH:26][C:27](O)=[CH:28][CH:29]=2)[CH2:24][CH2:23]1)[CH3:18].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[Cl:1][C:2]1[N:7]=[C:6]([NH:8][CH2:9][CH2:10][CH2:11][O:12][C:27]2[CH:26]=[C:25]3[C:30](=[CH:29][CH:28]=2)[C@H:22]([CH2:21][C:20]([O:19][CH2:17][CH3:18])=[O:32])[CH2:23][CH2:24]3)[C:5]([C:13]([F:16])([F:14])[F:15])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 11776TriphenylphosphineHCID 16110404ethyl 2-[(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetateHCID 593004473-{[6-Chloro-3-(trifluoromethyl)-2-pyridinyl]amino}-1-propanol

Product 1

HCID 59300543ethyl [(1S)-5-(3-{[6-chloro-3-(trifluoromethyl)-2-pyridinyl]amino}propoxy)-2,3-dihydro-1H-inden-1-yl]acetateYield 62%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 3-{[6-chloro-3-(trifluoromethyl)-2-pyridinyl]amino}-1-propanol (Example 302) (0.63 g, 2.45 mmol) and ethyl [(1S)-5-hydroxy-2,3-dihydro-1H-inden-1-yl]acetate (Example 6, 0.45 g, 2.05 mmol) in THF (6.80 mL) was added triphenylphosphine (0.70 g, 2.66 mmol) and 1,1′-azodicarbonyl)-dipiperidine (0.68 g, 2.66 mmol) under argon. The golden yellow mixture was stirred at rt for 18 h, and then concentrated under reduced pressure. The product (0.58 g, 62%) was isolated after column chromatography (2:1 hexanes/EtOAc). 1H NMR (400 MHz, CD3OD) δ 7.65 (d, 1H), 7.02 (d, 1H), 6.76 (d, 1H), 6.69 (dd, 1H), 6.60 (d, 1H), 6.48 (b, 1H), 4.15 (q, 2H), 4.04 (t, 2H), 3.65 (q, 2H), 3.46 (qt. 1H), 2.92-2.68 (m, 3H), 2.42-2.30 (m, 2H), 1.78-1.68 (m, 1H), 1.27 (t, 3H).

Workup

  1. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-7d8444f93991435dbbdd5e7c2d294e04
Source dataset
uspto-grants-2010_05
Patent number
US07714004B2

Reaction notes

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