tert-Butyl Formate → (S)-2-[(S)-2-(4-Allyloxy-3-chloro-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 928224Notes

Reaction equation

HRID 928224 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13]([OH:15])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16]([O:19][C:20]1[CH:25]=[CH:24][C:23]([CH2:26][C@H:27]([NH2:32])[C:28]([O:30][CH3:31])=[O:29])=[CH:22][C:21]=1[Cl:33])[CH:17]=[CH2:18].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C.C([O-])(O)=O.[Na+].C(OC(C)(C)C)=O>CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][C@H:9]1[C:13](=[O:15])[NH:32][C@H:27]([C:28]([O:30][CH3:31])=[O:29])[CH2:26][C:23]1[CH:24]=[CH:25][C:20]([O:19][CH2:16][CH:17]=[CH2:18])=[C:21]([Cl:33])[CH:22]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

8

Reactant 6

HCID 61207tert-Butyl FormateHCID 81531DiisopropylethylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 516892Sodium BicarbonateHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86691117(S)-methyl 3-(4-(allyloxy)-3-chlorophenyl)-2-aminopropanoate

Product 1

HCID 86691119(S)-2-[(S)-2-(4-Allyloxy-3-chloro-phenyl)-1-methoxycarbonyl-ethylcarbamoyl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
25 °C

Procedure

In a 25 mL round-bottomed flask, (S)-1-(tert-butoxycarbonyl)pyrrolidine-2-carboxylic acid (279 mg, 1.3 mmol, Eq: 1.00) and (S)-methyl 3-(4-(allyloxy)-3-chlorophenyl)-2-aminopropanoate (350 mg, 1.3 mmol, Eq: 1.00) were combined with DMF (6 mL) to give a colorless solution. HATU (986 mg, 2.59 mmol, Eq: 2.00) and Hunig's base (335 mg, 453 μL, 2.59 mmol, Eq: 2.00) were added. The reaction mixture was stirred at 25° C. for 20 h. The reaction mixture was poured into saturated aqueous NaHCO3 solution and extracted with DCM (2×). The organic layers were combined, washed with water (3×) and brine (1×). The organic layers were dried over Na2SO4 and concentrated in vacuo. The crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 3/1, 2/1) to yield a yellow oil (570 mg; 94%). m/z=467.2 [M+H]+; 367.1 [M+H-Boc]+.

Workup

  1. customto give a colorless solution
  2. extractionextracted with DCM (2×)
  3. washwashed with water (3×) and brine (1×)
  4. dry with materialThe organic layers were dried over Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe crude material was purified by flash chromatography (silica gel, 20 g, n-heptane/AcOEt 3/1, 2/1)
  7. customto yield a yellow oil (570 mg; 94%)

Sources & evidence

ORD record
ord-641eb06a6f2949f0853643f0b9c70710
Source dataset
uspto-grants-2016_03
Patent number
US09290467B2

Reaction notes

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