9-Fluorenylmethyl chloroformate → HCID 69432315, compound

HRID 458326Notes

Reaction equation

HRID 458326 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:23][NH:24][CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[F:33])=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(C(C)C)C(C)C)C.Cl[C:44]([O:46][CH2:47][CH:48]1[C:60]2[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=2[C:54]2[C:49]1=[CH:50][CH:51]=[CH:52][CH:53]=2)=[O:45].C([O-])(O)=O.[Na+]>C(Cl)Cl.CN(C1C=CN=CC=1)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([S:13][CH2:14][C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH2:10][C@H:9]1[CH2:23][N:24]([CH2:25][C:26]1[CH:31]=[C:30]([F:32])[CH:29]=[CH:28][C:27]=1[F:33])[C:44]([O:46][CH2:47][CH:48]1[C:49]2[CH:50]=[CH:51][CH:52]=[CH:53][C:54]=2[C:55]2[C:60]1=[CH:59][CH:58]=[CH:57][CH:56]=2)=[O:45])=[O:7])([CH3:4])([CH3:2])[CH3:3]

Participants

7

Reactant 4

HCID 343679-Fluorenylmethyl chloroformateHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 69432348HCID 69432348, compound

Product 1

HCID 69432315HCID 69432315, compoundYield 82%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6344DichloromethaneSolvent

Procedure

To 3.19 g (6.67 mmol, 1 eq) (2S,4R)-2-[(2,5-difluoro-benzylamino)-methyl]-4-(4-methoxy-benzylsulfanyl)-pyrrolidine-1-carboxylic acid tert-butyl ester in 10 ml CH2Cl2 were added 1.35 ml (8.0 mmol, 1.2 eq) EtNiPr2, followed by 2.07 g (8.0 mmol, 1.2 eq) 9-fluorenylmethyl chloroformate and a catalytic amount of DMAP at 0° C. The solution was stirred at room temperature overnight, 5% NaHCO3 solution was added (pH 9), the layers were separated and the inorganic one was extracted with CH2Cl2. The combined organic layers were washed with 1M KHSO4 and brine, dried over Na2SO4 and evaporated. The crude product was purified by flash chromatography with EtOAc/hexane 1:3 as eluent yielding 3.81 g (82%) (2S,4R)-2-{[(2,5-difluoro-benzyl)-(9H-fluoren-9-ylmethoxy-carbonyl)-amino]-methyl}-4-(4-methoxy-benzylsulfanyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as white foam, which was subjected to the next reaction directly.

Workup

  1. customat 0° C
  2. customthe layers were separated
  3. extractionthe inorganic one was extracted with CH2Cl2
  4. washThe combined organic layers were washed with 1M KHSO4 and brine
  5. dry with materialdried over Na2SO4
  6. customevaporated
  7. customThe crude product was purified by flash chromatography with EtOAc/hexane 1:3 as eluent

Sources & evidence

ORD record
ord-2195b3597e5f41f68072f0d89eab4ac9
Source dataset
uspto-grants-2007_03
Patent number
US07189756B2

Reaction notes

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