Water → N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanine pivaloyloxymethyl ester

HRID 1934396Notes

Reaction equation

HRID 1934396 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][CH:11](/[CH:14]=[CH:15]/[C:16]([N:18]2[CH2:23][CH2:22][CH2:21][C@@H:20]([C:24]([NH:26][C@H:27]([C:32]#[CH:33])[CH2:28][C:29]([OH:31])=[O:30])=[O:25])[CH2:19]2)=[O:17])[CH2:10][CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])([O-])=O.[K+].[K+].I[CH2:41][O:42][C:43](=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45].O>CN(C)C=O>[C:43]([O:42][CH2:41][O:30][C:29](=[O:31])[CH2:28][C@@H:27]([C:32]#[CH:33])[NH:26][C:24]([C@@H:20]1[CH2:21][CH2:22][CH2:23][N:18]([C:16](=[O:17])/[CH:15]=[CH:14]/[CH:11]2[CH2:10][CH2:9][N:8]([C:6]([O:5][C:1]([CH3:3])([CH3:2])[CH3:4])=[O:7])[CH2:13][CH2:12]2)[CH2:19]1)=[O:25])(=[O:48])[C:44]([CH3:47])([CH3:46])[CH3:45]

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 104401Iodomethyl pivalateHCID 86758027N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanine

Product 1

HCID 86758034N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-beta-alanine pivaloyloxymethyl esterYield 59.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine (0.5 g) in dimethylformamide (5 ml) was added K2CO3 (75 mg) under stirring at 0° C., stirred for 15 minutes, and pivalic acid iodomethyl ester (0.61 g) in dimethylformamide (3 ml) was added to the mixture. After stirring at room temperature for 1 hour, the mixture was poured into water and extracted with ethyl acetate. The extract was washed with water and brine, dried over MgSO41 and evaporated in vacuo, subsequently. The residue was purified by column chromatography on silica gel eluting with CHCl3:MeOH=(98:2) to give N-[(R)-1-[3-(1-tert-butoxycarbonyl-4-piperidyl)-(E)-acryloyl]-3-piperidylcarbonyl]-3(S)-ethynyl-β-alanine pivaloyloxymethyl ester as a colorless oil (0.37 g, 59.3%).

Workup

  1. stirringstirred for 15 minutes
  2. stirringAfter stirring at room temperature for 1 hour
  3. extractionextracted with ethyl acetate
  4. washThe extract was washed with water and brine
  5. customdried over MgSO41
  6. customevaporated in vacuo
  7. customThe residue was purified by column chromatography on silica gel eluting with CHCl3

Sources & evidence

ORD record
ord-f308b3b4c15948ba8230851d2e8c3a66
Source dataset
uspto-grants-2002_05
Patent number
US06384028B1

Reaction notes

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