Triphenylphosphine → HCID 178498039, compound

HRID 1050456Notes

Reaction equation

HRID 1050456 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CC(OC(/N=N/C(OC(C)C)=O)=O)C.[Cl:34][C:35]1[CH:36]=[C:37]([OH:46])[C:38]([CH3:45])=[C:39]([CH:44]=1)[C:40]([O:42][CH3:43])=[O:41].[CH2:47]([NH:54][C:55]([C@H:57]1[CH2:62][CH2:61][C@@H:60](O)[CH2:59][CH2:58]1)=[O:56])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1>C1COCC1>[CH2:47]([NH:54][C:55]([C@H:57]1[CH2:62][CH2:61][C@H:60]([O:46][C:37]2[C:38]([CH3:45])=[C:39]([CH:44]=[C:35]([Cl:34])[CH:36]=2)[C:40]([O:42][CH3:43])=[O:41])[CH2:59][CH2:58]1)=[O:56])[C:48]1[CH:53]=[CH:52][CH:51]=[CH:50][CH:49]=1

Participants

6

Reactant 4

HCID 11776TriphenylphosphineHCID 5363146Diisopropyl azodicarboxylateHCID 70904667Methyl 5-chloro-3-hydroxy-2-methylbenzoateHCID 178522831HCID 178522831, compound

Product 1

HCID 178498039HCID 178498039, compoundYield 34.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a cooled (0° C. ice bath) solution of triphenylphosphine (392 mg, 1.495 mmol) in THF (10 mL) was added DIAD (0.291 mL, 1.495 mmol). The reaction was stirred for 15 minutes (became a suspension). To this suspension with stirring was added a solution of methyl 5-chloro-3-hydroxy-2-methylbenzoate (250 mg, 1.246 mmol) and (cis)-N -benzyl-4-hydroxycyclohexanecarboxamide (350 mg, 1.500 mmol) in THF (5 mL) in one portion. The reaction was allowed to warm to room temperature and stirred overnight, at which time the reaction was concentrated in vacuo. The residue was purified by silica gel chromatography (Analogix, SF25-60 g, 10 to 60% EtOAc in hexanes). The resulting solid was triturated with 10% methanol in water, filtered, washed with water, and dried under vacuum to give methyl 3-(((trans)-4-(benzylcarbamoyl)cyclohexyl)oxy)-5-chloro-2-methylbenzoate (180 mg, 0.433 mmol, 34.7% yield) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ 8.33 (t, J=5.94 Hz, 1H), 7.38 (d, J=2.02 Hz, 1H), 7.27-7.35 (m, 3H), 7.16-7.27 (m, 3H), 4.37-4.49 (m, 1H), 4.27 (d, J=5.81Hz, 2H), 3.82 (s, 3H), 2.25 (s, 3H), 1.97-2.16 (m, 3H), 1.75-1.89 (m, 2H), 1.53-1.69 (m, 2H), 1.30-1.47 (m, 2H). MS(ES) [M+H]+ 259.0 (weak).

Workup

  1. stirringTo this suspension with stirring
  2. stirringstirred overnight, at which time the reaction
  3. concentrationwas concentrated in vacuo
  4. customThe residue was purified by silica gel chromatography (Analogix
  5. customThe resulting solid was triturated with 10% methanol in water
  6. filtrationfiltered
  7. washwashed with water
  8. customdried under vacuum

Sources & evidence

ORD record
ord-2fe972792b75417e9e9f85f08999b9e0
Source dataset
uspto-grants-2016_07
Patent number
US09382234B2

Reaction notes

Loading…