Diisopropylethylamine → (2S,4R)-tert-butyl 2-(N-(hex-5-enyl)-N-methyl-carbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 517016Notes

Reaction equation

HRID 517016 reaction equation
[C:1]([N:8]1[CH2:15][C@@H:14]([OH:16])[CH2:13][C@H:9]1[C:10]([OH:12])=O)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].F[B-](F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2C=CC=CC=2N=N1.S(C1C=CC(C)=CC=1)(O)(=O)=O.[CH3:50][NH:51][CH2:52][CH2:53][CH2:54][CH2:55][CH:56]=[CH2:57].CCN(C(C)C)C(C)C>CN(C=O)C>[CH2:52]([N:51]([CH3:50])[C:10]([C@@H:9]1[CH2:13][C@@H:14]([OH:16])[CH2:15][N:8]1[C:1]([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2])=[O:12])[CH2:53][CH2:54][CH2:55][CH:56]=[CH2:57]

Participants

6

Reactant 4

HCID 81531DiisopropylethylamineHCID 688614(2S,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acidHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 46737741N-methylhex-5-en-1-amine 4-methylbenzenesulfonate

Product 1

HCID 57816706(2S,4R)-tert-butyl 2-(N-(hex-5-enyl)-N-methyl-carbamoyl)-4-hydroxypyrrolidine-1-carboxylateYield 95%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a cold solution of cis-N-Boc-4-hydroxy-L-proline (10 g, 1 eq.), O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU 15.5 g, 1.12 eq.) and N-methylhex-5-en-1-amine tosylate salt 32a (13.6 g, 1.1 eq.), which was prepared according to Scheme 13 as described herein, in DMF (80 mL) containing DIPEA (29.4 mL, 3.9 eq.) was added dropwise under nitrogen at 0° C. The reaction mixture was stirred overnight at room temperature, and then quenched with water and extracted with diethyl ether. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel to yield compound 48 as a rose powder in 95% yield. 1H NMR (DMSO-d6, 400 MHz): δ (ppm) 1.29-1.3 (m, 9H), 1.33-1.55 (m, 4H), 1.70-1.80 (m, 1H), 1.97-2.12 (m, 3H), 2.77-2.97 (m, 3H), 3.15-3.40 (m, 4H), 4.22 (br s, 1H), 4.50-4.62 (m, 1H), 4.90-5.04 (m, 3H), 5.71-5.83 (m, 1H); MS (ESI+): m/z=327 (MH+).

Workup

  1. additionwas added dropwise under nitrogen at 0° C
  2. customquenched with water
  3. extractionextracted with diethyl ether
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by chromatography on silica gel

Sources & evidence

ORD record
ord-e1393e8e73da44408c883ec4f800a377
Source dataset
uspto-grants-2015_08
Patent number
US09115095B2

Reaction notes

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