Sodium Bicarbonate → (1R,2S)-1-({(2S,4R)-1-[(1S)-1-((1S,2R)-2-Acetoxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]-4-hydroxy-pyrrolidine-2-carbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid ethyl ester

HRID 1822465Notes

Reaction equation

HRID 1822465 reaction equation
[NH2:1][C@@H:2]([C:19]([CH3:22])([CH3:21])[CH3:20])[C:3]([NH:5][C@H:6]1[C:14]2[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH2:8][C@H:7]1[O:15][C:16](=[O:18])[CH3:17])=[O:4].[C:23]([O-])(O)=[O:24].[Na+].[CH2:28]([O:30][C:31]([C@:33]1([NH:38][C:39]([C@@H:41]2[CH2:45][C@@H:44]([OH:46])[CH2:43][NH:42]2)=[O:40])[CH2:35][C@@H:34]1[CH:36]=[CH2:37])=[O:32])[CH3:29]>C(#N)C>[CH2:28]([O:30][C:31]([C@@:33]1([NH:38][C:39]([C@@H:41]2[CH2:45][C@@H:44]([OH:46])[CH2:43][N:42]2[C:23](=[O:24])[NH:1][C@H:2]([C:3](=[O:4])[NH:5][C@H:6]2[C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[CH2:8][C@H:7]2[O:15][C:16](=[O:18])[CH3:17])[C:19]([CH3:22])([CH3:21])[CH3:20])=[O:40])[CH2:35][C@H:34]1[CH:36]=[CH2:37])=[O:32])[CH3:29]

Participants

5

Reactant 3

HCID 516892Sodium BicarbonateHCID 57892990Acetic acid (1S,2R)-1-((2S)-2-amino-3,3-dimethyl-butyrylamino)-indan-2-yl esterHCID 68409004(1S,2R)-1-[(2S,4R)-(4-Hydroxy-pyrrolidine-2-carbonyl)-amino]-2-vinyl-cyclopropanecarboxylic acid ethyl ester

Product 1

HCID 57892941(1R,2S)-1-({(2S,4R)-1-[(1S)-1-((1S,2R)-2-Acetoxy-indan-1-ylcarbamoyl)-2,2-dimethyl-propylcarbamoyl]-4-hydroxy-pyrrolidine-2-carbonyl}-amino)-2-vinyl-cyclopropanecarboxylic acid ethyl esterYield 80%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

To a stirred solution of compound 89 (1.81 g) in acetonitrile at 0° C. solid NaHCO3 (800 mg) and p-nitrophenychlorocarbonate (1.2 g) was added. The slurry was taken up to ambient temperature and stirred for another 30 min. To this slurry a solution of compound 91 (1.6 g) in acetonitrile (5 mL) diisopropylethylamine (1 mL) was added. After 10 min the resulting mixture was concentrated, re-dissolved in ethyl acetate and washed with K2CO3 (aq) and then with 0.5 N HCl. Dried and concentrated which gave a >80% pure product by HPLC M+H+599.6

Workup

  1. customwas taken up to ambient temperature
  2. concentrationAfter 10 min the resulting mixture was concentrated
  3. dissolutionre-dissolved in ethyl acetate
  4. washwashed with K2CO3 (aq)
  5. customDried
  6. concentrationconcentrated which

Sources & evidence

ORD record
ord-863d1e7942264f7184ed5bdac0c538c2
Source dataset
uspto-grants-2009_10
Patent number
US07608590B2

Reaction notes

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