Triethylamine → (2S,4S)-1-tert-butyl 2-methyl 4-azidopyrrolidine-1,2-dicarboxylate

HRID 1269006Notes

Reaction equation

HRID 1269006 reaction equation
[CH2:1](N(CC)CC)C.C[Si](N([Si](C)(C)C)C(=O)C(F)(F)F)(C)C.[C:23]([N:30]1[CH2:37][C@@H:36]([N:38]=[N+:39]=[N-:40])[CH2:35][C@H:31]1[C:32]([OH:34])=[O:33])([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C.ClC(Cl)C.CSC>[CH3:1][O:33][C:32](=[O:34])[C@@H:31]1[CH2:35][C@H:36]([N:38]=[N+:39]=[N-:40])[CH2:37][N:30]1[C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 65279N,N-Bis(trimethylsilyl)trifluoroacetamideHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12094910(2S,4S)-4-azido-1-[(tert-butoxy)carbonyl]pyrrolidine-2-carboxylic acid

Product 1

HCID 11219435(2S,4S)-1-tert-butyl 2-methyl 4-azidopyrrolidine-1,2-dicarboxylateYield 90%

Reagents, catalysts & solvents 3

HCID 1068Dimethyl SulfideSolventHCID 6228DimethylformamideSolventHCID 63651,1-DichloroethaneSolvent

Procedure

1-(2-(S)-4-(S)-(Azido)-N-pyrrolidin-2-yl-{1-(R)-[2-(S),3-(S),4-(S),5-(R)-trihydroxy-6-(R)-(methylsulfanyl)tetrahydropyran-2-yl]-2-hydroxy-prop-1-yl}acetamide. To 2b (R9′=H) (200 mg, 0.788 mmol) in DMF (5 mL) at 0° C., triethylamine (0.164 mL, 1.18 mmol) and bis-(trimethylsilyl)trifluoroacetamide (0.93 mL, 3.94 mmol) were added and then left stirring at room temperature overnight. After which, N-Boc-(2S,4S)-4-azidoproline (300 mg, 1.18 mmol) and HATU (444 mg, 1.18 mmol) was added at 0° C. and then left stirring for four hours. At the end, DMF was removed and the residue was taken in ethyl acetate (100 mL) and washed with citric acid (10%, 30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL). After drying the organic portion with sodium sulfate, the solvent was removed to obtain the crude product which was taken as such for the next deprotection step. To the crude product in dichloroethane 30% trifluoroacetic acid (10 mL) and dimethylsulfide (0.5 mL) was added and the reaction mixture was stirred for an hour. The solvent was removed and the crude product obtained was chromatographed on silica gel column using 20% methanol in DCM to obtain the title compound as a white solid (278 mg, 90%): TLC: Rf=0.38 (40% methanol in DCM); 1H NMR (300 MHz, CD3OD) δ 4.24 (d, J=5.4, 1), 4.16 (s, 1), 4.03–4.13 (m, 3), 3.95 (d, J=3.6, 1), 3.80 (dd, J=4.5, 9.9, 1), 3.51–3.56 (dd, J=3.3, 10.2, 1), 3.13–3.22 (m, 1), 2.95–3.00 (m, 1), 2.35–2.45 (m, 1), 2.08 (s, 3), 1.93–2.04 (m, 1), 1.29 (t, J=7.2, 1), 0.97 (m, 3); MS (ESPOS): 392 [M+H]+.

Workup

  1. waitleft
  2. waitleft
  3. stirringstirring for four hours
  4. customAt the end, DMF was removed
  5. washwashed with citric acid (10%, 30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL)
  6. dry with materialAfter drying the organic portion with sodium sulfate
  7. customthe solvent was removed
  8. customto obtain the crude product which
  9. stirringthe reaction mixture was stirred for an hour
  10. customThe solvent was removed
  11. customthe crude product obtained
  12. customwas chromatographed on silica gel column

Sources & evidence

ORD record
ord-2f7d3c841147465cbdc379783cb51b1e
Source dataset
uspto-grants-2007_04
Patent number
US07199106B2

Reaction notes

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