Diisopropylethylamine → (R)-tert-Butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylate

HRID 1253747Notes

Reaction equation

HRID 1253747 reaction equation
C(N(C(C)C)C(C)C)C.[Cl:10][C:11]1[CH:31]=[CH:30][CH:29]=[CH:28][C:12]=1[C:13]([NH:15][C@H:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25](O)=[O:26])[CH:23]=2)[CH2:18][CH2:17]1)=[O:14].O.ON1C2C=CC=CC=2N=N1.[CH2:43]1[C:48]2([CH2:53][CH2:52][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:50][CH2:49]2)[CH2:47][CH2:46][CH2:45][NH:44]1>C(Cl)Cl>[Cl:10][C:11]1[CH:31]=[CH:30][CH:29]=[CH:28][C:12]=1[C:13]([NH:15][C@H:16]1[C:24]2[C:19](=[CH:20][CH:21]=[C:22]([C:25]([N:44]3[CH2:45][CH2:46][CH2:47][C:48]4([CH2:49][CH2:50][N:51]([C:54]([O:56][C:57]([CH3:60])([CH3:59])[CH3:58])=[O:55])[CH2:52][CH2:53]4)[CH2:43]3)=[O:26])[CH:23]=2)[CH2:18][CH2:17]1)=[O:14]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 27960291-Hydroxybenzotriazole hydrateHCID 46912008tert-Butyl 2,9-diazaspiro(5.5)undecane-9-carboxylateHCID 59505489(3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid

Product 1

HCID 59505373(R)-tert-Butyl 2-(3-(2-chlorobenzamido)-2,3-dihydro-1H-indene-5-carbonyl)-2,9-diazaspiro[5.5]undecane-9-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

N-Ethyl-diisopropylamine (4 eq.) was added to a solution of (3R)-3-[(2-chloro-benzoyl)amino]-2,3-dihydro-1H-indene-5-carboxylic acid (E-03) (0.952 mmol, 1 eq.) in methylene chloride (18 ml). The reaction mixture was cooled to 0° C. and N-ethyl-N′-3-(dimethylamino)-propyl-carbodiimide hydrochloride (1.2 eq.) and 1-hydroxybenzotriazole hydrate (0.2 eq.) were then added. The mixture was stirred at this temperature for 15 min, before tert-butyl 2,9-diazaspiro[5.5]undecane-9-carboxylate (1.1 eq.) was added. The reaction mixture was stirred at room temperature for 2.5 d. Then, the reaction mixture was washed in each case 1× with 10% NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution. The organic phase was dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography (silica; ethyl acetate/hexane/ammonia (25 aq.) 70:10:0.8). Yield: 70%

Workup

  1. additionwas added
  2. washThen, the reaction mixture was washed in each case 1× with 10% NH4Cl solution, sat. NaHCO3 solution and sat. NaCl solution
  3. dry with materialThe organic phase was dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by column chromatography (silica; ethyl acetate/hexane/ammonia (25 aq.) 70:10:0.8)

Sources & evidence

ORD record
ord-92adf253362e4655aeac303b64e1f4f3
Source dataset
uspto-grants-2013_06
Patent number
US08455475B2

Reaction notes

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