Dicyclohexylcarbodiimide → HCID 9932935, compound

HRID 1683187Notes

Reaction equation

HRID 1683187 reaction equation
C1(N=C=NC2CCCCC2)CCCCC1.[F:16][C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1[CH:23]1[NH:27][C@H:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25][S:24]1.[C:35]([O:39][C:40]([NH:42][CH2:43][C:44](O)=[O:45])=[O:41])([CH3:38])([CH3:37])[CH3:36]>C(#N)C>[C:35]([O:39][C:40]([NH:42][CH2:43][C:44]([N:27]1[C@H:26]([C:28]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH2:25][S:24][C@@H:23]1[C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[F:16])=[O:45])=[O:41])([CH3:38])([CH3:37])[CH3:36]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 78288N-(tert-butoxycarbonyl)glycineHCID 22870470HCID 22870470, compound

Product 1

HCID 9932935HCID 9932935, compoundYield 64.3%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

(2R,4R)-tert-Butyl 3-(2-tert-butoxycarbonylamino)-2-(2-fluorophenyl)-thiazolidine-4-carboxylate can be prepared in the following manner: a solution of 18.2 g of N,N'-dicyclohexylcarbodiimide in 75 cm3 of anhydrous acetonitrile is added over 30 minutes to a solution of 25.0 g of (2RS,4R)-tert-butyl 2-(2-fluorophenyl)thiazolidine-4-carboxylate and of 15.5 g of 2-tert-butoxycarbonylaminoacetic acid in 150 cm3 of anhydrous acetonitrile, maintained at a temperature close to 0° C. The reaction mixture is stirred for 16 hours at a temperature close to 25° C. The insoluble product is separated off by filtration, washed with 3 times 20 cm3 of acetonitrile, and the filtrate is concentrated to dryness at reduced pressure at 40° C. The crude product obtained is purified by chromatography on silica [eluent: ethyl acetatecyclohexane (30-70 by volume)]. The fractions containing the expected product are combined and concentrated to dryness at reduced pressure at 40° C. 25.0 g of (2R,4R)-tert-butyl 3-(2-tert-butoxycarbonylaminoacetyl)-2-(2-fluorophenyl)thiazolidine-4-carboxylate are thus obtained in the form of an oil, which is employed as it is in the subsequent syntheses.

Workup

  1. temperaturemaintained at a temperature
  2. customclose to 0° C
  3. customclose to 25° C
  4. customThe insoluble product is separated off by filtration
  5. washwashed with 3 times 20 cm3 of acetonitrile
  6. concentrationthe filtrate is concentrated to dryness at reduced pressure at 40° C
  7. customThe crude product obtained
  8. customis purified by chromatography on silica [eluent: ethyl acetatecyclohexane (30-70 by volume)]
  9. additionThe fractions containing the expected product
  10. concentrationconcentrated to dryness at reduced pressure at 40° C

Sources & evidence

ORD record
ord-225005aa899f4eac86f96c1892cb1f72
Source dataset
uspto-grants-1997_06
Patent number
US05637602

Reaction notes

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