Diisopropyl azodicarboxylate → tert-Butyl (3S)-3-[4-({3-[4-(phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenoxy]pyrrolidine-1-carboxylate

HRID 401663Notes

Reaction equation

HRID 401663 reaction equation
[C:1]1([C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:18][N:17]([C:19]([C:21]4[CH:26]=[CH:25][C:24]([OH:27])=[CH:23][CH:22]=4)=[O:20])[CH2:16]3)[CH2:11][CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:28]([N:35]1[CH2:42][CH2:41][CH:40](O)[C@@H:36]1C(O)=O)([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29].CC(OC(/N=N/C(OC(C)C)=O)=O)C>C1COCC1>[C:1]1([C:7]([N:9]2[CH2:14][CH2:13][N:12]([CH:15]3[CH2:18][N:17]([C:19]([C:21]4[CH:22]=[CH:23][C:24]([O:27][C@H:41]5[CH2:40][CH2:36][N:35]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:42]5)=[CH:25][CH:26]=4)=[O:20])[CH2:16]3)[CH2:11][CH2:10]2)=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

5

Reactant 3

HCID 5363146Diisopropyl azodicarboxylateHCID 20609990(R)-N-Boc-3-hydroxyprolineHCID 596258104-({3-[4-(Phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenol

Product 1

HCID 59625931tert-Butyl (3S)-3-[4-({3-[4-(phenylcarbonyl)piperazin-1-yl]azetidin-1-yl}carbonyl)phenoxy]pyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of compound 26d (100 mg, 0.273 mmol) and (R)—N-Boc-3-hydroxyproline in THF was added DIAD at 0° C. The resulting reaction mixture was stirred for 18 h. After dilution with water and extraction with EtOAc (3×), the combined organic extracts were dried over Na2SO4, filtered, and concentrated under reduced pressure. The resultant residue was purified by flash column chromatography on silica gel using 5% MeOH/CH2Cl2 to give compound 434 (95 mg). 1H NMR (CDCl3): δ 7.52 (d, J=8.6 Hz, 2H), 7.37-7.44 (m, 5H), 7.24-7.29 (m, 3H), 7.18-7.24 (m, 3H), 4.18-4.33 (m, 2H), 4.09-4.17 (m, 3H), 4.01-4.08 (m, 1H), 3.92 (br. S, 1H), 3.74 (br. s., 1H), 3.35-3.63 (m, 2H), 3.17-3.29 (m, 1H), 2.20-2.50 (m, 4H); MS m/z (M+H+) 506.0.

Workup

  1. customThe resulting reaction mixture
  2. extractionAfter dilution with water and extraction with EtOAc (3×)
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe resultant residue was purified by flash column chromatography on silica gel using 5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-52d20ef593e040c196dc1bb99118038d
Source dataset
uspto-grants-2014_06
Patent number
US08741887B2

Reaction notes

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