Sodium borohydride → (3R,4R)-benzyl 3-amino-4-(tosyloxy)piperidine-1-carboxylate

HRID 451802Notes

Reaction equation

HRID 451802 reaction equation
[BH4-].[Na+].[N:3]([C@@H:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[O:13])[CH2:8][C@H:7]1[O:22][S:23]([C:26]1[CH:32]=[CH:31][C:29]([CH3:30])=[CH:28][CH:27]=1)(=[O:25])=[O:24])=[N+]=[N-].[N:33]([C@H:36]1[C@H:41]([O:42][S:43]([C:46]2[CH:52]=[CH:51][C:49]([CH3:50])=[CH:48][CH:47]=2)(=[O:45])=[O:44])[CH2:40][CH2:39][N:38]([C:53]([O:55][CH2:56][C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[O:54])[CH2:37]1)=[N+]=[N-]>CO>[NH2:3][C@@H:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)=[O:13])[CH2:8][C@H:7]1[O:22][S:23]([C:26]1[CH:27]=[CH:28][C:29]([CH3:30])=[CH:31][CH:32]=1)(=[O:25])=[O:24].[NH2:33][C@H:36]1[C@H:41]([O:42][S:43]([C:46]2[CH:47]=[CH:48][C:49]([CH3:50])=[CH:51][CH:52]=2)(=[O:44])=[O:45])[CH2:40][CH2:39][N:38]([C:53]([O:55][CH2:56][C:57]2[CH:58]=[CH:59][CH:60]=[CH:61][CH:62]=2)=[O:54])[CH2:37]1

Participants

6

Reactant 3

HCID 4311764Sodium borohydride2×HCID 59201561HCID 59201561, compoundHCID 59201713HCID 59201713, compound

Product 2

HCID 59201302trans-Benzyl 4-amino-3-(tosyloxy)piperidine-1-carboxylateHCID 59201320(3R,4R)-benzyl 3-amino-4-(tosyloxy)piperidine-1-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent2×

Procedure

To a 0° C. solution of CuSO4.5H2O (642 mg, 0.5 equiv) in methanol (30 mL), NaBH4 (200 mg, 1.05 equiv) was added. To the stirred black suspension was added a solution of trans-benzyl 4-azido-3-(tosyloxy)piperidine-1-carboxylate and trans-benzyl 3-azido-4-(tosyloxy)piperidine-1-carboxylate (2.21 g, 5.14 mmol) in methanol (20 mL). Additional NaBH4 (578 mg, 3 equiv) was added in four portions over the course of 1 h. The reaction mixture was filtered through a pad of Celite and concentrated. The residue was diluted with CH2Cl2 (70 mL), washed with water (15 mL), satd aq NH4Cl solution (2×10 mL), brine (15 mL), and dried over Na2SO4. Concentration afforded trans-benzyl 4-amino-3-(tosyloxy)piperidine-1-carboxylate and trans-benzyl 3-amino-4-(tosyloxy)piperidine-1-carboxylate (1.34 g, 64%). The product was used for the next step without further purification. MS ESI +ve m/z 405 (M+1).

Workup

  1. filtrationThe reaction mixture was filtered through a pad of Celite
  2. concentrationconcentrated
  3. additionThe residue was diluted with CH2Cl2 (70 mL)
  4. washwashed with water (15 mL)
  5. dry with materialdried over Na2SO4
  6. concentrationConcentration

Sources & evidence

ORD record
ord-4ab17a4660de47e1916bf15986aacd5f
Source dataset
uspto-grants-2013_07
Patent number
US08487108B2

Reaction notes

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