Hydrogen iodide → HCID 59238168, compound

HRID 2068588Notes

Reaction equation

HRID 2068588 reaction equation
[CH2:1]([O:8][C:9]([N:11]1[CH2:16][CH:15]2[CH2:17][CH:12]1[CH2:13][C:14]2([C:19]1[CH:20]=[C:21]2[C:26](=[CH:27][CH:28]=1)[N:25]=[CH:24][N:23]([CH2:29][C:30]([O:32]CC)=[O:31])[C:22]2=[O:35])O)=[O:10])C1C=CC=CC=1.I.C(Cl)(OC[CH:41]1[C:53]2[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=2)[C:47]2[C:42]1=[CH:43][CH:44]=[CH:45][CH:46]=2)=O>CC(O)=O>[CH:43]1[C:42]2[CH:41]([CH2:1][O:8][C:9]([N:11]3[CH2:16][CH:15]4[CH2:17][CH:12]3[CH2:13][CH:14]4[C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[N:25]=[CH:24][N:23]([CH2:29][C:30]([OH:32])=[O:31])[C:22]4=[O:35])=[O:10])[C:53]3[C:48](=[CH:49][CH:50]=[CH:51][CH:52]=3)[C:47]=2[CH:46]=[CH:45][CH:44]=1

Participants

5

Reactant 3

HCID 24841Hydrogen iodideHCID 343679-Fluorenylmethyl chloroformateHCID 59238175HCID 59238175, compound

Product 1

HCID 59238168HCID 59238168, compoundYield 42%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

To a mixture of 13 (22.4 g, 47 mmol) in HOAc (448 mL) was added HI (268 mL). The mixture was heated to reflux at 120° C. overnight. The reaction mixture was evaporated and its pH was adjusted to 6-7 with potassium carbonate and NaHCO3. Then 50 mL of tetrahydrofuran was added. To the mixture was added FmocCl (15.68 g, 61 mmol) and stirred at room temperature for 5 h. Then the reaction mixture was extracted with ethyl acetate and washed with water 3 times. The organic layer was dried over sodium sulfate, filtered and evaporated to dryness. Purification by chromatography (eluant:methylene chloride to methylene chloride/MeOH/HAc 8/1/0.1) gave 10.3 g of crude 5-(3-carboxymethyl-4-oxo-3,4-dihydro-quinazolin-6-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid 9H-fluoren-9-ylmethyl ester which was further purified by preparative HPLC to give 2.7 g of pure 5-(3-carboxymethyl-4-oxo-3,4-dihydro-quinazolin-6-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid 9H-fluoren-9-ylmethyl ester (11% yield in 2 steps).

Workup

  1. temperatureThe mixture was heated
  2. customThe reaction mixture was evaporated
  3. additionThen 50 mL of tetrahydrofuran was added
  4. extractionThen the reaction mixture was extracted with ethyl acetate
  5. washwashed with water 3 times
  6. dry with materialThe organic layer was dried over sodium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness
  9. customPurification by chromatography (eluant:methylene chloride to methylene chloride/MeOH/HAc 8/1/0.1)

Sources & evidence

ORD record
ord-d6bb614dad9b4472914feadf8f99db7c
Source dataset
uspto-grants-2012_10
Patent number
US08299023B2

Reaction notes

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