Triphenylphosphine → HCID 59541185, compound

HRID 1874247Notes

Reaction equation

HRID 1874247 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). 1H 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, 2 H), 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-929e5346f0c24df08929f53f75b25d70
Source dataset
uspto-grants-2012_11
Patent number
US08304403B2

Reaction notes

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