Ammonium Acetate → (R)-tert-butyl 2-(amino(4-(benzyloxy)phenyl)methyl)pyrrolidine-1-carboxylate

HRID 1874646Notes

Reaction equation

HRID 1874646 reaction equation
[CH2:1]([O:8][C:9]1[CH:28]=[CH:27][C:12]([C:13]([C@H:15]2[CH2:19][CH2:18][CH2:17][N:16]2[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])=O)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([O-])(=O)C.[NH4+].[B-]C#[N:36].[Na+]>CO>[NH2:36][CH:13]([C:12]1[CH:27]=[CH:28][C:9]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)=[CH:10][CH:11]=1)[C@H:15]1[CH2:19][CH2:18][CH2:17][N:16]1[C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21]

Participants

5

Reactant 3

HCID 517165Ammonium AcetateHCID 20587905Sodium cyanoborohydride [MI]2×HCID 58466416HCID 58466416, compound

Product 1

HCID 67437465(R)-tert-butyl 2-(amino(4-(benzyloxy)phenyl)methyl)pyrrolidine-1-carboxylateYield 100%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

A solution of (R)-tert-butyl 2-(4-(benzyloxy)benzoyl)pyrrolidine-1-carboxylate (247 mg, 0.648 mmol) and dry ammonium acetate (399 mg, 5.18 mmol) in methanol (13.0 mL) was stirred at room temperature for 30 min. To this was added sodium cyanotrihydroborate (81 mg, 1.295 mmol) and the reaction mixture heated to 60° C. for 24 h. An additional portion of sodium cyanotrihydroborate (81 mg, 1.30 mmol) was added and the heating continued at 60° C. for 48 h. The reaction solution was cooled to room temperature, quenched with water and extracted with ethyl acetate (3×). The combined organic layers were washed with brine, dried over MgSO4, filtered and concentrated. The residue was purified by column chromatography on silica gel (5%→60% ethyl acetate in hexanes). Obtained (R)-tert-butyl 2-(amino(4-(benzyloxy)phenyl)methyl)pyrrolidine-1-carboxylate (100 mg, 0.262 mmol, 100% yield) as a slightly yellow oil that was carried on without further purification. 1H NMR (400 MHz, CDCl3) δ 7.27-7.46 (m, 5H), 6.90-7.15 (m, 4H), 4.97-5.14 (m, 2H), 4.10-4.53 (m, 1H), 3.27-3.64 (m, 1H), 2.55-2.78 (m, 1H), 2.26-2.45 (m, 1H), 1.54-2.11 (m, 4H), 1.45-1.54 (m, 9H); LRMS (ESI) m/e 383.13, 404.11 [(M+H)+, calcd for C23H31N2O3 383.23].

Workup

  1. temperatureThe reaction solution was cooled to room temperature
  2. customquenched with water
  3. extractionextracted with ethyl acetate (3×)
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified by column chromatography on silica gel (5%→60% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-7df55cf44a544d95b3035f6b4bf990a4
Source dataset
uspto-grants-2012_11
Patent number
US08304577B2

Reaction notes

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