1,1'-Carbonyldiimidazole → Ethyl 2-(7-bromo-1'-((1-hydroxy-4-adamantyl)carbamoyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate

HRID 1424622Notes

Reaction equation

HRID 1424622 reaction equation
[NH2:1][CH:2]1[CH:9]2[CH2:10][C:5]3([OH:12])[CH2:6][CH:7]([CH2:11][CH:3]1[CH2:4]3)[CH2:8]2.C1N=CN([C:18]([N:20]2[CH:24]=N[CH:22]=[CH:21]2)=[O:19])C=1.CCN(C(C)C)C(C)C.[Br:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:48]=1[C:42]1(CCNC[CH2:43]1)[CH2:41][CH:40]2[CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51]>C(Cl)Cl>[Br:34][C:35]1[CH:36]=[CH:37][CH:38]=[C:39]2[C:48]=1[C:42]1([CH2:22][CH2:21][N:20]([C:18](=[O:19])[NH:1][CH:2]3[CH:9]4[CH2:10][C:5]5([OH:12])[CH2:6][CH:7]([CH2:11][CH:3]3[CH2:4]5)[CH2:8]4)[CH2:24][CH2:43]1)[CH2:41][CH:40]2[CH2:49][C:50]([O:52][CH2:53][CH3:54])=[O:51]

Participants

6

Reactant 4

HCID 682631,1'-CarbonyldiimidazoleHCID 81531DiisopropylethylamineHCID 28574474-Aminoadamantan-1-olHCID 58137336Ethyl 2-(7-bromo-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate

Product 1

HCID 66954318Ethyl 2-(7-bromo-1'-((1-hydroxy-4-adamantyl)carbamoyl)-2,3-dihydrospiro[indene-1,4'-piperidine]-3-yl)acetate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-aminoadamantan-1-ol (628 mg, 3.76 mmol) in dry CH2Cl2 (2 mL) was added CDI (736 mg, 4.52 mmol) and DIEA (3.24 g, 25.12 mmol) at 0° C. under N2 and the mixture was stirred for 1 h. Ethyl 2-(7-bromo-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate (1.10 g, 3.14 mmol) was added and the mixture was stirred overnight. The mixture was washed with 5% aq HCl, and the organic layer was concentrated to give the crude product. Purification by preparative TLC followed by preparative HPLC gave two isomers of ethyl 2-(7-bromo-1′-((1-hydroxy-4-adamantyl)carbamoyl)-2,3-dihydrospiro[indene-1,4′-piperidine]-3-yl)acetate.

Workup

  1. stirringthe mixture was stirred overnight
  2. washThe mixture was washed with 5% aq HCl
  3. concentrationthe organic layer was concentrated
  4. customto give the crude product
  5. customPurification by preparative TLC

Sources & evidence

ORD record
ord-adc6b5acfc50488991317bfff572602d
Source dataset
uspto-grants-2015_01
Patent number
US08927715B2

Reaction notes

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