Chloroacetic Acid → (2R,3R)-3-(2-Chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 449829Notes

Reaction equation

HRID 449829 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@H:10]([OH:13])[C@H:9]1[CH2:14][N:15]1[C:23]2[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=2[C:17]2[CH2:26][C@H:27]([NH:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][C:16]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:36][CH2:37][C:38](O)=[O:39].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][C@@H:10]([O:13][C:38](=[O:39])[CH2:37][Cl:36])[C@H:9]1[CH2:14][N:15]1[C:23]2[CH:22]=[CH:21][C:20]([C:24]#[N:25])=[CH:19][C:18]=2[C:17]2[CH2:26][C@H:27]([NH:29][C:30]([O:32][CH:33]([CH3:35])[CH3:34])=[O:31])[CH2:28][C:16]1=2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 300Chloroacetic AcidHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 66933249(2R,3S)-2-((S)-7-Cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 86651083(2R,3R)-3-(2-Chloro-acetoxy)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 54%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of (2R,3S)-2-((S)-7-cyano-2-isopropoxycarbonylamino-2,3-dihydro-1H-cyclopenta[b]indol-4-ylmethyl)-3-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (950 mg, 1.97 mmol), chloroacetic acid (227 mg, 2.36 mmol), and triphenylphosphine (626 mg, 2.36 mmol) in tetrahydrofuran (20 mL) is treated with diethyl azodicarboxylate (374 μL, 2.36 mmol) dropwise at room temperature. The reaction mixture is stirred overnight. The reaction is diluted with ethyl acetate (50 mL) and then washed with water and brine. The organic portion is dried over sodium sulfate and concentrated. The resulting residue is purified by medium pressure liquid chromatography, eluting with ethyl acetate:hexane (1:1). Fractions containing pure product are combined and concentrated to afford 0.59 g (54%) of the title compound. LC-ES/MS m/z 581.0 [M+Na]+, TR=4.46 min.

Workup

  1. washwashed with water and brine
  2. dry with materialThe organic portion is dried over sodium sulfate
  3. concentrationconcentrated
  4. customThe resulting residue is purified by medium pressure liquid chromatography
  5. washeluting with ethyl acetate:hexane (1:1)
  6. additionFractions containing pure product
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-90fcf7ab9c5344a5b8b86ce11469e227
Source dataset
uspto-grants-2013_07
Patent number
US08486943B2

Reaction notes

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