Iodine → (S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 2212125Notes

Reaction equation

HRID 2212125 reaction equation
N(C(OCC)=O)=NC(OCC)=O.[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25]O)=[O:19])([CH3:16])([CH3:15])[CH3:14].[I:27]I.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[C:13]([O:17][C:18]([N:20]1[CH2:24][CH2:23][CH2:22][C@H:21]1[CH2:25][I:27])=[O:19])([CH3:16])([CH3:15])[CH3:14]

Participants

6

Reactant 4

HCID 807IodineHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 643448(S)-(-)-N-Boc-prolinol

Product 1

HCID 11312942(S)-2-Iodomethyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 76.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under a nitrogen atmosphere, a solution of diethyl azodicarboxylate (4.699 g, 26.98 mmol) in dry tetrahydrofuran (THF) (15 mL) was added drop-wise to an ice-cold stirring solution of (2S)-N-(tert-butoxycarbonyl)-2-(hydroxymethyl)pyrrolidine (5.37 g, 26.7 mmol), iodine (3.42 g, 13.5 mmol) and triphenylphosphine (7.069 g, 26.95 mmol) in dry THF (50 mL). The mixture was stirred and allowed to warm to ambient temperature overnight. The mixture was concentrated on a rotary evaporator and then the residue was stirred with 5% aqueous Na2S2O3 (50 mL). After stirring for 30 min, the mixture was extracted with dichloromethane (4×25 mL). The combined dichloromethane extracts were dried (Na2SO4), filtered and concentrated. The residue was repeatedly crystallized (three to four times) from dry ether and finally from heptane to give 3.20 g (38.6%) of product.

Workup

  1. concentrationThe mixture was concentrated on a rotary evaporator
  2. stirringthe residue was stirred with 5% aqueous Na2S2O3 (50 mL)
  3. stirringAfter stirring for 30 min
  4. extractionthe mixture was extracted with dichloromethane (4×25 mL)
  5. dry with materialThe combined dichloromethane extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was repeatedly crystallized (three to four times) from dry ether

Sources & evidence

ORD record
ord-456a65fded804563812c90c65da05e4e
Source dataset
uspto-grants-2006_09
Patent number
US07101896B2

Reaction notes

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