tert-Butanol → [(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

HRID 587406Notes

Reaction equation

HRID 587406 reaction equation
[CH2:1]([N:8]1[CH2:12][C@@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[C@H:10](C(O)=O)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC[N:26]([CH:30](C)C)C(C)C.C1(P(N=[N+]=[N-])(C2C=CC=CC=2)=[O:40])C=CC=CC=1.[C:50]([OH:54])([CH3:53])([CH3:52])[CH3:51]>>[C:50]([O:54][C:30](=[O:40])[NH:26][C@H:10]1[C@H:11]([C:13]2[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([F:20])[CH:14]=2)[CH2:12][N:8]([CH2:1][C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=2)[CH2:9]1)([CH3:53])([CH3:52])[CH3:51]

Participants

5

Reactant 4

HCID 6386tert-ButanolHCID 81531DiisopropylethylamineHCID 199401P,P-Diphenylphosphinic azideHCID 58303139(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acid

Product 1

HCID 58303063[(3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidin-3-yl]-carbamic acid tert-butyl ester

Conditions

Temperature
55 °C

Procedure

A mixture of 15.1 g (41 mmol) (3S,4R)-1-Benzyl-4-(4-chloro-3-fluoro-phenyl)-pyrrolidine-3-carboxylic acid and 11.6 g (90 mmol) DIPEA in 100 mL t-butanol was heated to 55° C. and 12.4 g (45 mmol) diphenylphosphoryl azide was added. The mixture was heated to 80° C. for 3 h and evaporated. The residue was subjected to column chromatography on silica eluting with a gradient formed from ethyl acetate and heptane to yield after evaporation of the product containing fractions 5.7 g (34%) of the title compound as off-white solid. MS m/e: 405.3 [M+H]+.

Workup

  1. temperatureThe mixture was heated to 80° C. for 3 h
  2. customevaporated
  3. customformed from ethyl acetate and heptane
  4. customto yield
  5. customafter evaporation of the product
  6. additioncontaining fractions 5.7 g (34%) of the title compound as off-white solid

Sources & evidence

ORD record
ord-a30ec14d911d48d380f673d202f6fa38
Source dataset
uspto-grants-2016_01
Patent number
US09226916B2

Reaction notes

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