Triphenylphosphine → HCID 59541185, compound

HRID 1712790Notes

Reaction equation

HRID 1712790 reaction equation
[CH:1]1([NH:6][C:7]([NH:9][C:10]([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:40])([F:39])[F:38])[CH:31]=2)([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=2)[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([OH:18])=[CH:14][CH:13]=2)=[O:8])[CH2:5][CH2:4][CH2:3][CH2:2]1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O[CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][C:66]([O:68][CH2:69][CH3:70])=[O:67].CCOC(/N=N/C(OCC)=O)=O>C1COCC1>[CH:1]1([NH:6][C:7](=[O:8])[NH:9][C:10]([C:19]2[CH:24]=[CH:23][CH:22]=[C:21]([O:25][C:26]([F:29])([F:28])[F:27])[CH:20]=2)([C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([O:36][C:37]([F:38])([F:39])[F:40])[CH:31]=2)[CH2:11][C:12]2[CH:17]=[CH:16][C:15]([O:18][CH2:61][CH2:62][CH2:63][CH2:64][CH2:65][C:66]([O:68][CH2:69][CH3:70])=[O:67])=[CH:14][CH:13]=2)[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 357781Ethyl 6-hydroxyhexanoateHCID 5462977Diethyl azodicarboxylateHCID 59459049HCID 59459049, compound

Product 1

HCID 59541185HCID 59541185, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an oven-dried 3-necked 10 mL round-bottom flask under nitrogen was added 1-cyclopentyl-3-(2-(4-hydroxyphenyl)-1,1-bis(3-(trifluoromethoxy)phenyl)ethyl)urea, prepared as described in Procedure 11, 6, 2 and 59, (50 mg, 0.1 mmol), triphenylphosphine (34 mg, 0.1 mmol), ethyl 6-hydroxyhexanoate (17 mg, 0.1 mmol) and dry THF (0.5 mL). The reaction mixture was cooled in an ice-methanol bath and diethylazodicarboxylate (23 mg, 0.13 mmol) was added via syringe. The reaction was allowed to warm to rt and stirred overnight. The reaction mixture was concentrated in vacuo and purified by ISCO silica gel chromatography using a gradient of 5-25% EtOAc/hexanes as eluent to yield ethyl 6-(4-(2-(3-cyclopentylureido)-2,2-bis(3-(trifluoromethoxy)phenyl)ethyl)phenoxy)hexanoate (Example 313) was isolated as a white solid (43 mg, 61% yield). HPLC: RT=4.69 minutes (Phenomenex Luna C18 5μ column 4.6×50 mm eluting with 10-90% aqueous methanol containing 0.1% phosphoric acid over a 4 minute gradient monitoring at 220 nm). LC/MS [M+H] 711.3 (Phenomenex Luna C18 5μ, column 4.6×30 mm eluting with 10-90% aqueous methanol containing 0.1% TFA over a 4 minute gradient monitoring at 220 nm). NMR (400 MHz, CDCl3) δ ppm 7.33 (t, J=7.9 Hz, 2H), 7.20 (d, J=7.9 Hz, 2H), 7.12 (d, J=7.9 Hz, 2H), 7.07 (s, 2H), 6.62 (d, J=8.8 Hz, 2H), 6.56 (d, J=8.8 Hz, 2H), 4.10 (q, J=7.1 Hz, 2H), 3.86 t, J=6.1 Hz, 2H), 3.68 (s, 1H), 3.62 (t, J=6.6 Hz, 1H), 2.30-2.27 (m, 2H), 1.82-1.14 (m, 17H), 1.23 (t, J=7.1 Hz, 3H).

Workup

  1. customprepared
  2. temperatureThe reaction mixture was cooled in an ice-methanol bath
  3. concentrationThe reaction mixture was concentrated in vacuo
  4. custompurified by ISCO silica gel chromatography

Sources & evidence

ORD record
ord-06f03011fa19400ab5af37085d76dba0
Source dataset
uspto-grants-2010_09
Patent number
US07790770B2

Reaction notes

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