Dimethylamine → (2S,4R)-tert-butyl 2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

HRID 1581711Notes

Reaction equation

HRID 1581711 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([OH:16])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].C[CH2:18][N:19](C(C)C)[CH:20](C)C.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.CNC>C(Cl)Cl>[C:1]([O:5][C:6]([N:8]1[CH2:12][C@H:11]([OH:13])[CH2:10][C@H:9]1[C:14]([N:19]([CH3:20])[CH3:18])=[O:16])=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 674DimethylamineHCID 81531DiisopropylethylamineHCID 88804(2S,4R)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acidHCID 151348Benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate

Product 1

HCID 25180889(2S,4R)-tert-butyl 2-(dimethylcarbamoyl)-4-hydroxypyrrolidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of 11.2 g of (2S,4R)-1-(tert-butoxycarbonyl)-4-hydroxy-2-pyrrolidinecarboxylic acid in 50 ml of DCM is cooled to 0° C., 8.45 ml of DIPEA and then 21.2 g of BOP are added and the resulting mixture is stirred for 10 minutes. Dimethylamine gas is then added by sparging and the mixture is stirred for 3 hours at RT. The reaction mixture is partially concentrated under vacuum to a volume of 20 ml and an insoluble material is filtered off. The filtrate is chromatographed on silica gel, eluting with a DCM/MeOH mixture (94/6; v/v) and the product obtained is re-chromatographed on alumina, eluting with a DCM/MeOH mixture (96/4; v/v). 11.1 g of the expected product are obtained.

Workup

  1. customby sparging
  2. stirringthe mixture is stirred for 3 hours at RT
  3. concentrationThe reaction mixture is partially concentrated under vacuum to a volume of 20 ml
  4. filtrationan insoluble material is filtered off
  5. customThe filtrate is chromatographed on silica gel
  6. washeluting with a DCM/MeOH mixture (94/6; v/v)
  7. customthe product obtained
  8. customis re-chromatographed on alumina
  9. washeluting with a DCM/MeOH mixture (96/4; v/v)

Sources & evidence

ORD record
ord-597a9b6e06fb44febfbc6c311c7bc73c
Source dataset
uspto-grants-2004_05
Patent number
US06730695B2

Reaction notes

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