Potassium Carbonate → tert-butyl (1S,2S)-1-benzyl-2-hydroxy-4-({(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanoyl}amino)-5-[4-(2-pyridinyl)phenyl]pentylcarbamate

HRID 1174306Notes

Reaction equation

HRID 1174306 reaction equation
[CH3:1][O:2][C:3]([NH:5][C@@H:6]([C:10]([CH3:13])([CH3:12])[CH3:11])[C:7]([OH:9])=O)=[O:4].C([O-])([O-])=O.[K+].[K+].CCOP(ON1N=NC2C=CC=CC=2C1=O)(OCC)=O.[C:40]([O:44][C:45]([NH:47][C@@H:48]([CH2:77][C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1)[C@@H:49]([OH:76])[CH2:50][CH:51]([NH:65]C(=O)OCC1C=CC=CC=1)[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][N:60]=2)=[CH:55][CH:54]=1)=[O:46])([CH3:43])([CH3:42])[CH3:41]>C(OCC)(=O)C>[CH2:77]([C@H:48]([NH:47][C:45](=[O:46])[O:44][C:40]([CH3:42])([CH3:41])[CH3:43])[C@@H:49]([OH:76])[CH2:50][CH:51]([NH:65][C:7](=[O:9])[C@@H:6]([NH:5][C:3]([O:2][CH3:1])=[O:4])[C:10]([CH3:13])([CH3:12])[CH3:11])[CH2:52][C:53]1[CH:58]=[CH:57][C:56]([C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][N:60]=2)=[CH:55][CH:54]=1)[C:78]1[CH:83]=[CH:82][CH:81]=[CH:80][CH:79]=1

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 42939953-(Diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-oneHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 86726220Benzyl (3S,4S)-4-[(tert-butoxycarbonyl)amino]-3-hydroxy-5-phenyl-1-[4-(2-pyridinyl)benzyl]pentylcarbamate

Product 1

HCID 86726221tert-butyl (1S,2S)-1-benzyl-2-hydroxy-4-({(2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanoyl}amino)-5-[4-(2-pyridinyl)phenyl]pentylcarbamate

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (2S)-2-[(methoxycarbonyl)amino]-3,3-dimethylbutanoic acid (Degussa, 8.74 g, 46.18 mmol, 1.1 equivalents), K2CO3 (11.60 g, 83.96 mmol, 2equivalents), DEPBT (15.08 g, 50.38 mmol, 1.2 equivalents) in ethyl acetate (400 mL) was stirred at room temperature under N2 for 1 hour, treated with the product of Example 111-11 (20 g, 41.98 mmol) and stirred at room temperature under N2 for 24 hrs. The reaction mixture was washed with H2O (200 mL), 10% NaHCO3 (200 mL), and H2O (2×200 mL). The organic layer was concentrated, and the residue charged with ethyl acetate (30 mL), heated to 70° C. for 1 hr, added heptanes (120 mL) dropwise, stirred at 70° C. for 30 minutes, cooled to room temperature overnight. The slurry was filtered and washed with 100 mL of 1:1 heptane/ethyl acetate, and dried in 50° C. vacuum oven overnight to give the title compound.

Workup

  1. stirringstirred at room temperature under N2 for 24 hrs
  2. washThe reaction mixture was washed with H2O (200 mL), 10% NaHCO3 (200 mL), and H2O (2×200 mL)
  3. concentrationThe organic layer was concentrated
  4. additionthe residue charged with ethyl acetate (30 mL)
  5. temperatureheated to 70° C. for 1 hr
  6. additionadded heptanes (120 mL) dropwise
  7. stirringstirred at 70° C. for 30 minutes
  8. temperaturecooled to room temperature overnight
  9. filtrationThe slurry was filtered
  10. washwashed with 100 mL of 1:1 heptane/ethyl acetate
  11. customdried in 50° C. vacuum oven overnight

Sources & evidence

ORD record
ord-58aa21911a5f4b42b4504097d79128cc
Source dataset
uspto-grants-2010_11
Patent number
US07834043B2

Reaction notes

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