Di-benzoyl-d-tartaric acid → (r)-Tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate dibenzoyl-d-tartaric acid salt

HRID 1694573Notes

Reaction equation

HRID 1694573 reaction equation
[CH:1]1[C:10]2[C:5](=[C:6]([NH:11][CH:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1.[C:24]([C@:32]([C:47]([OH:49])=[O:48])([OH:46])[C@:33]([C:38](=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([OH:37])[C:34]([OH:36])=[O:35])(=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>CC(O)C>[C:38]([C@:33]([C:34]([OH:36])=[O:35])([OH:37])[C@:32]([C:24](=[O:31])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1)([OH:46])[C:47]([OH:49])=[O:48])(=[O:45])[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[CH:1]1[C:10]2[C:5](=[C:6]([NH:11][C@@H:12]3[CH2:16][CH2:15][N:14]([C:17]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])=[O:18])[CH2:13]3)[CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][N:2]=1

Participants

4

Reactant 2

HCID 12362977Di-benzoyl-d-tartaric acidHCID 23079381Tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate

Product 1

HCID 131729631(r)-Tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate dibenzoyl-d-tartaric acid saltYield 44.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent2×

Conditions

Temperature
42 °C

Procedure

Salt Formation: To a 5 L flask equipped with an internal temperature probe, a heating mantle and a mechanical stirrer were added tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate (250 g, 0.798 mol, from Example 1) and 3 L of 2-propanol. The mixture was stirred and warmed to 42° C. to form a homogeneous solution. To the stirred solution was added dibenzoyl-D-tartaric acid (D-DBTA) (242.9 g, 0.678 mol) in one portion and another 0.9 L of 2-propanol. The mixture was stirred at 40° C. for 15 minutes to form a solution. The mixture was stirred at 40° C. to form a yellow slurry. The slurry was cooled to 30° C. The suspension was filtered, washed with 2×250 mL of 2-propanol and dried in a vacuum oven at ˜35° C. Approximately 204.3 g of (R)-tert-butyl 3-(isoquinolin-5-ylamino)pyrrolidine-1-carboxylate dibenzoyl-D-tartaric acid salt crude product was obtained as a yellow solid (84% ee, 38% yield).

Workup

  1. customSalt Formation: To a 5 L flask equipped with an internal temperature probe
  2. customto form a homogeneous solution
  3. stirringThe mixture was stirred at 40° C. for 15 minutes
  4. customto form a solution
  5. stirringThe mixture was stirred at 40° C.
  6. customto form a yellow slurry
  7. temperatureThe slurry was cooled to 30° C
  8. filtrationThe suspension was filtered
  9. washwashed with 2×250 mL of 2-propanol
  10. customdried in a vacuum oven at ˜35° C

Sources & evidence

ORD record
ord-69f56cc0ae4d4bd4a24a68d9b656055b
Source dataset
uspto-grants-2012_04
Patent number
US08158796B2

Reaction notes

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