4-Methylmorpholine → benzyl N-[1-(hydroxymethyl)cyclohexyl]carbamate

HRID 276250Notes

Reaction equation

HRID 276250 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1([C:18](O)=[O:19])[CH2:17][CH2:16][CH2:15][CH2:14][CH2:13]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CN1CCOCC1.ClC(OCC(C)C)=O.[BH4-].[Na+]>COCCOC.O>[CH2:1]([O:8][C:9]([NH:11][C:12]1([CH2:18][OH:19])[CH2:13][CH2:14][CH2:15][CH2:16][CH2:17]1)=[O:10])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 79724-MethylmorpholineHCID 62365Isobutyl chloroformateHCID 4311764Sodium borohydrideHCID 113578861-(Cbz-amino)cyclohexanecarboxylic acid

Product 1

HCID 18316421benzyl N-[1-(hydroxymethyl)cyclohexyl]carbamateYield 101.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
4 °C

Procedure

To a solution of 1-(benzyloxycarbonylamino)cyclohexane-1-carboxylic acid (4.16 g, 15.0 mmol) and N-methylmorpholine (1.81 mL, 16.5 mmol) in DME (15 mL) at 4° C. was slowly added isobutyl chloroformate (2.14 mL, 16.5 mmol) and the reaction mixture was stirred for 5 min, then filtered into a pre-cooled (4° C.) flask. Sodium borohydride (0.85 g, 22.5 mmol) in water (7 mL) wag added followed immediately by water (500 mL). The reaction was then warmed to 20° C. and stirred for 30 min. The reaction mixture was extracted with CH2Cl2 and concentrated under reduced pressure to yield 1-(benzyloxycarbonylamino)-1-(hydroxymethyl)cyclohexane (4.0 g, 100%): TLC (25% EtOAc/hex) Rf0.11.

Workup

  1. customat 4° C.
  2. filtrationfiltered into
  3. temperatureThe reaction was then warmed to 20° C.
  4. stirringstirred for 30 min
  5. extractionThe reaction mixture was extracted with CH2Cl2
  6. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-13d53586dd804c1483413dab09c6a654
Source dataset
uspto-grants-2002_03
Patent number
US06353006B1

Reaction notes

Loading…