Lithium Hydroxide → HCID 178445891, compound

HRID 84207Notes

Reaction equation

HRID 84207 reaction equation
[OH:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.C([O:33][C:34](=[O:54])[C:35]([CH3:53])([CH3:52])[CH2:36][C@H:37]([NH2:51])[CH2:38][C:39]1[CH:44]=[CH:43][C:42]([C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)=[CH:41][CH:40]=1)C.[Li+].[OH-]>CN(C=O)C.O.C1COCC1.CO>[C:42]1([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[CH:41]=[CH:40][C:39]([CH2:38][C@@H:37]([NH:51][C:7]([C:5]2[O:4][N:3]=[C:2]([OH:1])[CH:6]=2)=[O:9])[CH2:36][C:35]([CH3:53])([CH3:52])[C:34]([OH:54])=[O:33])=[CH:44][CH:43]=1

Participants

10

Reactant 5

HCID 3939Lithium HydroxideHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 68180969(R)-4-Amino-5-biphenyl-4-yl-2,2-dimethyl-pentanoic acid ethyl esterHCID 178524642HCID 178524642, compound

Product 1

HCID 178445891HCID 178445891, compound

Reagents, catalysts & solvents 4

HCID 887MethanolSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolvent

Procedure

3-Hydroxyisoxazole-5-carboxylic acid (396 mg, 307 μmol, 1.0 eq.), EDCI (54.4 μL, 307 μmol, 1.0 eq.) and HOBt (41.5 mg, 307 μmol, 1.0 eq.) were combined in DMF (0.2 mL) and stirred for 5 minutes at room temperature. (R)-4-Amino-5-biphenyl-4-yl-2,2-dimethyl-pentanoic acid ethyl ester (100 mg, 307 μmol, 1.0 eq.) was added and the resulting mixture was stirred for 30 minutes. 1 M LiOH in water (1.2 mL) in THF (3 mL) was added and the mixture was maintained at 60° C. for 2 days. A small amount of MeOH was added to speed up the reaction. The reaction was then quenched with AcOH and the product was purified by preparative HPLC to yield the title compound (25 mg, 95% purity. MS m/z [M+H]+ calc'd for C23H24N2O5, 409.17; Found 409.4.

Workup

  1. stirringthe resulting mixture was stirred for 30 minutes
  2. temperaturethe mixture was maintained at 60° C. for 2 days
  3. customthe reaction
  4. customThe reaction was then quenched with AcOH
  5. customthe product was purified by preparative HPLC

Sources & evidence

ORD record
ord-5eae6da57cbd4a43a933c1dfabf0ff7b
Source dataset
uspto-grants-2014_09
Patent number
US08846913B2

Reaction notes

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