4-Methylmorpholine → HCID 70566328, compound

HRID 1680566Notes

Reaction equation

HRID 1680566 reaction equation
[C:1]([NH:8][C@@H:9]([C:14]([OH:16])=O)[CH2:10][CH2:11][S:12][CH3:13])([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].CN1CCOCC1.C(OC(Cl)=O)C(C)C.Cl.[NH2:33][CH2:34][C:35]([NH:37][C@H:38]([C:46]([CH:48]1[C:55]2([NH2:57])[CH2:56][CH:51]3[CH2:52][CH:53]([CH2:58][C:49]1([C:59]([O:61][CH3:62])=[O:60])[CH2:50]3)[CH2:54]2)=[O:47])[CH2:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=1)=[O:36]>O1CCCC1.C(OCC)(=O)C>[C:1]([NH:8][C@@H:9]([C:14]([NH:33][CH2:34][C:35]([NH:37][C@H:38]([C:46]([CH:48]1[C:55]2([NH2:57])[CH2:56][CH:51]3[CH2:52][CH:53]([CH2:58][C:49]1([C:59]([O:61][CH3:62])=[O:60])[CH2:50]3)[CH2:54]2)=[O:47])[CH2:39][C:40]1[CH:41]=[CH:42][CH:43]=[CH:44][CH:45]=1)=[O:36])=[O:16])[CH2:10][CH2:11][S:12][CH3:13])([O:3][C:4]([CH3:5])([CH3:6])[CH3:7])=[O:2]

Participants

7

Reactant 4

HCID 79724-Methylmorpholine2×HCID 62365Isobutyl chloroformateHCID 111051N-(tert-Butyloxycarbonyl)-D-methionineHCID 70565612HCID 70565612, compound

Product 1

HCID 70566328HCID 70566328, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

A mixed anhydride is prepared by reacting 2.0 g of Boc-D-methionine with 0.90 ml of N-methylmorpholine and 1.06 ml isobutylchloroformate in 15 ml of tetrahydrofuran at -20° C. A solution of 2.84 g of methyl glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate hydrochloride in 15 ml tetrahydrofuran is neutralized with 0.78 ml N-methyl morpholine and added to the mixed anhydride reaction above. The reaction mixture is stirred for 2 hours at room temperature and allowed to stand overnight. The reaction mixture is diluted with 200 ml of ethyl acetate. The ethyl acetate layer is collected and washed with water, followed by washes with 0.2 M potassium bisulfate, water, and 1 M potassium bicarbonate and dried over magnesium sulfate. The solution is filtered and the solvent removed under reduced pressure. Purification of the residue by low pressure chromatography on silica gel affords methyl Boc-D-methionyl-glycyl-L-phenylalanyl-3-amino-1-adamantanecarboxylate which is represented by the following formula ##STR17##

Workup

  1. customat -20° C
  2. waitto stand overnight
  3. customThe ethyl acetate layer is collected
  4. washwashed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationThe solution is filtered
  7. customthe solvent removed under reduced pressure
  8. customPurification of the residue by low pressure chromatography on silica gel

Sources & evidence

ORD record
ord-fa350e6f18c44fa3ae7d19b80579269c
Source dataset
uspto-grants-1981_06
Patent number
US04273704

Reaction notes

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