Tert-Butylamine → Boc-Hyp-NH-tBu

HRID 741614Notes

Reaction equation

HRID 741614 reaction equation
C([O:8][C@@H:9]1[CH2:13][N:12]([C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[C@H:11]([C:21]([NH:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:10]1)C1C=CC=CC=1.CCN(C(C)C)C(C)C.C(N)(C)(C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1>C(Cl)Cl.CCOC(C)=O>[C:24]([NH:23][C:21]([C@@H:11]1[CH2:10][C@@H:9]([OH:8])[CH2:13][N:12]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[O:22])([CH3:27])([CH3:26])[CH3:25]

Participants

7

Reactant 4

HCID 6385Tert-ButylamineHCID 81531Diisopropylethylamine2×HCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphateHCID 103849174(S)-Benzyloxy-N-tert-butyl-1-(tert-butyloxycarbonyl) pyrrolidine-2(S)-carboxamide

Product 1

HCID 10334194Boc-Hyp-NH-tBuYield 72%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

The N-protected acid (17.5 g, 75.6 mmol, described in section (a) of example 1) was dissolved in CH2Cl2 (300 mL) and DIEA (13 mL, 76.6 mmol). tert-Butylamine (8.73 mL, 83.1 mmol ) was added to the solution, followed by the addition of BOP (40 g, 90.7 mmol) and DIEA (13 mL, 151 mmol). The mixture was stirred at room temperature for 7 h and then diluted with EtOAc. The organic phase was separated, washed with a saturated aqueous solution of NaHCO3 (2×), H2O (2×) and brine (2×), dried (MgSO4) and evaporated to dryness. The solid residue was triturated with Et2O/EtOAc (9:1), collected on a filter, washed with Et2O and dried to provide N-tert-butyl-1-(tert-butyloxycarbonyl)-4(R)-hydroxypyrrolidine-2(S)-carboxamide (15.6 g, 72%).

Workup

  1. customThe organic phase was separated
  2. washwashed with a saturated aqueous solution of NaHCO3 (2×), H2O (2×) and brine (2×)
  3. dry with materialdried (MgSO4)
  4. customevaporated to dryness
  5. customThe solid residue was triturated with Et2O/EtOAc (9:1)
  6. customcollected on a filter
  7. washwashed with Et2O
  8. customdried

Sources & evidence

ORD record
ord-e9b9078d35c4422887267e6d450778c3
Source dataset
uspto-grants-1996_09
Patent number
US05552405

Reaction notes

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