1-Chloroethyl chloroformate → (5R,7R)-4-(4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

HRID 529111Notes

Reaction equation

HRID 529111 reaction equation
[N+:1]([C:4]1[CH:52]=[CH:51][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[C:40]5[C:35](=[C:36]([CH2:41][NH:42][C:43]([O:45][C:46]([CH3:49])([CH3:48])[CH3:47])=[O:44])[CH:37]=[CH:38][CH:39]=5)[C:22]5([CH2:27][CH2:26][N:25](CC6C=CC=CC=6)[CH2:24][CH2:23]5)[CH2:21]4)[C:14]=3[C@H:13]([CH3:50])[CH2:12]2)=[O:9])=[CH:6][CH:5]=1)([O-:3])=[O:2].C(Cl)(=O)OC(Cl)C>C1(C)C=CC=CC=1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([C:8]([O:10][C@H:11]2[C:15]3[N:16]=[CH:17][N:18]=[C:19]([N:20]4[C:40]5[C:35](=[C:36]([CH2:41][NH:42][C:43]([O:45][C:46]([CH3:47])([CH3:48])[CH3:49])=[O:44])[CH:37]=[CH:38][CH:39]=5)[C:22]5([CH2:23][CH2:24][NH:25][CH2:26][CH2:27]5)[CH2:21]4)[C:14]=3[C@H:13]([CH3:50])[CH2:12]2)=[O:9])=[CH:51][CH:52]=1)([O-:3])=[O:2]

Participants

4

Reactant 2

HCID 5213051-Chloroethyl chloroformateHCID 68759150(5R,7R)-4-(1'-benzyl-4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

Product 1

HCID 69812199(5R,7R)-4-(4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,4'-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a stirred solution of (5R,7R)-4-(1′-benzyl-4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate (30 mg, 0.043 mmol) in toluene (1 mL) was added 1-chloroethyl carbonochloridate (0.009 mL, 0.08 mmol) at about 0° C. The reaction mixture was heated at reflux for 1 h and then evaporated in vacuo. The residue was dissolved in MeOH (1 mL) and the mixture was heated at reflux for 1 h. After cooling, the solvent was evaporated in vacuo to give crude (5R,7R)-4-(4-((tert-butoxycarbonylamino)methyl)spiro[indoline-3,4′-piperidine]-1-yl)-5-methyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-7-yl 4-nitrobenzoate, which was used in the next step without further purification. LCMS (APCI+) m/z 615 [M+H]+; Rt=3.31 min.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 1 h
  3. customevaporated in vacuo
  4. dissolutionThe residue was dissolved in MeOH (1 mL)
  5. temperaturethe mixture was heated
  6. temperatureat reflux for 1 h
  7. temperatureAfter cooling
  8. customthe solvent was evaporated in vacuo

Sources & evidence

ORD record
ord-41c0cd9a857247a68787f99dc311a223
Source dataset
uspto-grants-2016_05
Patent number
US09346805B2

Reaction notes

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