Methanol → HCID 59164823, compound

HRID 418367Notes

Reaction equation

HRID 418367 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:14]=[CH:13][C:12]([C@@H:15]3[NH:19][C@H:18]([C:20]([O:22]C)=[O:21])[CH2:17][CH2:16]3)=[CH:11][CH:10]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CO.[O:26](C(OC(C)(C)C)=O)[C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=O>C1COCC1.O>[CH3:31][C:30]([O:29][C:27]([N:19]1[C@@H:15]([C:12]2[CH:11]=[CH:10][C:9]([O:8][CH2:7][C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)=[CH:14][CH:13]=2)[CH2:16][CH2:17][C@H:18]1[C:20]([OH:22])=[O:21])=[O:26])([CH3:33])[CH3:32]

Participants

6

Reactant 3

HCID 887MethanolHCID 90495Di-tert-butyl dicarbonateHCID 59164839HCID 59164839, compound

Product 1

HCID 59164823HCID 59164823, compoundYield 90.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of methyl(5R)-5-{4-[(phenylmethyl)oxy]phenyl}-L-prolinate (120 mg, 0.38 mmol) in THF (2.3 ml) was added LiOH monohydrate (26 mg, 0.61 mmol) dissolved in water (1.1 ml), followed by methanol (1.1 ml). The resulting solution was stirred at room temperature for 2.5 hours, then left overnight at −18° C. Then the organic solvent was evaporated under reduced pressure maintaining the temperature at 38° C. and the aqueous residue containing the acid intermediate (Rt (HPLC)=3.63 min. MS: (ES/+) m/z: 298 [MH+]. C18H19NO3 requires 297) was treated with BOC2O (168 mg, 0.77 mmol) dissolved in THF (1.1 ml). The reaction mixture was stirred at room temperature for 3.5 hours. The organic solvent was evaporated and the basic aqueous solution was acidified at 0° C. with aqueous 1N HCl solution to pH=3, this acidic aqueous solution was extracted with ethyl acetate (2×10 ml). The organic phase dried over Na2 SO4 and evaporated under reduced pressure gave a solid, which was titurated in n-hexanes (3×6 ml) affording the title compound as a white powder (137 mg, 90% for two steps); Rt (HPLC): 5.81 min; Rf (cyclohexane:ethyl acetate=1:1): 0.34; MS: (ES/+) m/z: 420 [M+Na+]C23H27NO5 requires 397; MS: (ES/−) m/z: 396 [M-H]C23H27NO5 requires 397; 1H NMR (300 MHz, CDCl3) δ(ppm): 7.5-7.3 (m, 5H), 7.10 (bm, 2H), 6.90 (d, 2H), 5.08 (s, 2H), 4.65 (bm, 1H), 4.50 (bm, 1H), 2.58 (bm, 1H), 2.31 (bm, 1H), 2.11-1.90 (m, 2H), 1.16 (s, 9H).

Workup

  1. waitleft overnight at −18° C
  2. customThen the organic solvent was evaporated under reduced pressure
  3. temperaturemaintaining the temperature at 38° C.
  4. additionthe aqueous residue containing the acid intermediate (Rt (HPLC)=3.63 min
  5. stirringThe reaction mixture was stirred at room temperature for 3.5 hours
  6. customThe organic solvent was evaporated
  7. customwas acidified at 0° C. with aqueous 1N HCl solution to pH=3
  8. extractionthis acidic aqueous solution was extracted with ethyl acetate (2×10 ml)
  9. customThe organic phase dried over Na2 SO4
  10. customevaporated under reduced pressure
  11. customgave a solid, which

Sources & evidence

ORD record
ord-92a7225d40ce41ec93b4384889714791
Source dataset
uspto-grants-2012_01
Patent number
US08093268B2

Reaction notes

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