Diisopropylethylamine → 2-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate

HRID 1424630Notes

Reaction equation

HRID 1424630 reaction equation
[N:1]1([C:16]([O:18][CH:19]2[CH:26]3[CH2:27][CH:22]4[CH2:23][CH:24]([CH2:28][CH:20]2[CH2:21]4)[CH2:25]3)=[O:17])[CH2:6][CH2:5][C:4]2([C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[CH2:9][NH:8][CH2:7]2)[CH2:3][CH2:2]1.[CH2:29]([O:31][C:32]([C@@H:34]1[CH2:36][C@H:35]1[C:37](O)=[O:38])=[O:33])[CH3:30].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCOC(C)=O.C(Cl)Cl>[CH2:29]([O:31][C:32]([C@@H:34]1[CH2:36][C@H:35]1[C:37]([N:8]1[CH2:7][C:4]2([CH2:5][CH2:6][N:1]([C:16]([O:18][CH:19]3[CH:20]4[CH2:28][CH:24]5[CH2:23][CH:22]([CH2:27][CH:26]3[CH2:25]5)[CH2:21]4)=[O:17])[CH2:2][CH2:3]2)[C:15]2[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=2)[CH2:9]1)=[O:38])=[O:33])[CH3:30]

Participants

7

Reactant 4

HCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 11535603(1R,2R)-2-(ethoxycarbonyl)cyclopropane-1-carboxylic acidHCID 250646132-adamantyl 2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylate

Product 1

HCID 581372502-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4'-piperidine]-1'-carboxylateYield 69.1%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-Adamantyl 2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (12 mg, 0.025 mmol), trans-2-(ethoxycarbonyl)cyclopropanecarboxylic acid (8 mg, 2.5 equiv), HATU (11 mg, 1.15 equiv), DIEA (13 μL, 3 equiv) were mixed with CH2Cl2 (2 mL) and put on shaker for 1 h at rt. The mixture was diluted with EtOAc (8 mL), washed with 3% aq HCl (2×3 mL), concentrated and purified by preparative HPLC to afford 2-adamantyl 2-((1R,2R)-2-(ethoxycarbonyl)cyclopropanecarbonyl)-2,3-dihydro-1H-spiro[isoquinoline-4,4′-piperidine]-1′-carboxylate (9 mg, 69%).

Workup

  1. washwashed with 3% aq HCl (2×3 mL)
  2. concentrationconcentrated
  3. custompurified by preparative HPLC

Sources & evidence

ORD record
ord-a559383004f84c9dbb0511ec89b315a9
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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