Phenol → (S)-Tert-Butyl 3-phenoxypyrrolidine-1-carboxylate

HRID 341554Notes

Reaction equation

HRID 341554 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[OH:15][C@@H:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1.[C:28]1(O)[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1COCC1>[O:15]([C@H:16]1[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17]1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 996PhenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 6544479tert-Butyl (3R)-3-hydroxypyrrolidine-1-carboxylate

Product 1

HCID 69333485(S)-Tert-Butyl 3-phenoxypyrrolidine-1-carboxylateYield 63.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Diisopropyl azodicarboxylate (1.19 g, 5.87 mmol) was added to an ice cooled mixture of tert-butyl (3R)-3-hydroxypyrrolidine-1-carboxylate (1 g, 5.34 mmol), phenol (0.5 g, 5.34 mmol) and triphenylphosphine (1.5 g, 5.8 mmol) in THF (14 mL). The mixture was stirred at room temperature for 20 h. The mixture was then concentrated under vacuum and the residue was twice triturated with diethyl ether. The resultant solid was filtered off and discarded. The filtrate was washed with 1M aq. sodium hydroxide, dried over sodium sulfate and concentrated. The residue was purified by FCC, eluting with 10% EtOAc in heptane to afford the title compound (0.893 g, 63%). Method B HPLC-MS: MH+ requires m/z=208 Found: m/z=208, Rt=2.20 min (91%).

Workup

  1. temperaturecooled
  2. concentrationThe mixture was then concentrated under vacuum
  3. customthe residue was twice triturated with diethyl ether
  4. filtrationThe resultant solid was filtered off
  5. washThe filtrate was washed with 1M aq. sodium hydroxide
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated
  8. customThe residue was purified by FCC
  9. washeluting with 10% EtOAc in heptane

Sources & evidence

ORD record
ord-760638249bf4451885ee616ad2bbc83c
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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