(2R)-1-aminopropan-2-ol → N-[(2R)-2-Hydroxypropyl]-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxamide

HRID 909643Notes

Reaction equation

HRID 909643 reaction equation
[CH3:1][O:2][CH2:3][C@H:4]([CH3:31])[O:5][C:6]1[CH:7]=[C:8]([C:23]2[NH:27][C:26]([C:28](O)=[O:29])=[CH:25][CH:24]=2)[CH:9]=[C:10]([O:12][Si:13]([CH:20]([CH3:22])[CH3:21])([CH:17]([CH3:19])[CH3:18])[CH:14]([CH3:16])[CH3:15])[CH:11]=1.[NH2:32][CH2:33][C@H:34]([OH:36])[CH3:35].[Cl-].COC1N=C(OC)N=C([N+]2(C)CCOCC2)N=1>CO>[OH:36][C@H:34]([CH3:35])[CH2:33][NH:32][C:28]([C:26]1[NH:27][C:23]([C:8]2[CH:9]=[C:10]([O:12][Si:13]([CH:14]([CH3:15])[CH3:16])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:18])[CH3:19])[CH:11]=[C:6]([O:5][C@@H:4]([CH3:31])[CH2:3][O:2][CH3:1])[CH:7]=2)=[CH:24][CH:25]=1)=[O:29]

Participants

5

Reactant 3

HCID 439938(2R)-1-aminopropan-2-olHCID 27340594-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chlorideHCID 666835375-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid

Product 1

HCID 66681565N-[(2R)-2-Hydroxypropyl]-5-{3-[(1S)-2-methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxamideYield 84%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

5-{3-[(1S)-2-Methoxy-1-methylethoxy]-5-[(triisopropylsilyl)oxy]phenyl}-1H-pyrrole-2-carboxylic acid (51.4 g, 115 mmol) synthesized in Example (106c) was dissolved in methanol (600 mL), and (R)-(−)-1-amino-2-propanol (19.9 mL, 253 mmol) and 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride n hydrate (63.7 g, 230 mmol) were added, followed by stirring for 15 hours under nitrogen atmosphere. The solvent was distilled off under reduced pressure, and water (500 mL) was added, followed by extraction twice with ethyl acetate (500 mL). Subsequently, the organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the resulting residue was purified using silica gel column chromatography (elution solvent: ethyl acetate/hexane=25%-67%) to afford the desired compound (48.7 g, yield 84%) as a white solid.

Workup

  1. distillationThe solvent was distilled off under reduced pressure, and water (500 mL)
  2. additionwas added
  3. extractionfollowed by extraction twice with ethyl acetate (500 mL)
  4. washSubsequently, the organic layer was washed with saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. distillationThe solvent was distilled off under reduced pressure
  7. customthe resulting residue was purified
  8. washsilica gel column chromatography (elution solvent: ethyl acetate/hexane=25%-67%)

Sources & evidence

ORD record
ord-a6ac5da58c2d4616890b91321f2b2aa1
Source dataset
uspto-grants-2011_09
Patent number
US08017610B2

Reaction notes

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