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Hydrochloric Acid → (S,R) 1-Morpholin-2-yl-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

HRID 899085
Notes
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Reaction equation

HRID 899085 reaction equation
C([N:8]1[CH2:13][CH2:12][O:11][CH:10]([C:14]([C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=2)([OH:27])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH2:9]1)C1C=CC=CC=1.[ClH:34].C(O)C.C1(C)C=CC=CC=1>CO.[Pd]>[ClH:34].[NH:8]1[CH2:13][CH2:12][O:11][C@@H:10]([C@:14]([C:28]2[CH:29]=[CH:30][CH:31]=[CH:32][CH:33]=2)([OH:27])[CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[O:22][C:23]([F:26])([F:25])[F:24])[CH2:9]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 702EthanolHCID 1140TolueneHCID 692922931-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol

Product 1

HCID 69292906(S,R) 1-Morpholin-2-yl-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

Reagents, catalysts & solvents 2

HCID 23938
Palladium
Catalyst
HCID 887MethanolSolvent3×

Conditions

Temperature
40 °C

Procedure

Alternatively, the following method may be used. A stainless steel Buchi hydrogenation reactor was loaded with 1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol (230 g, 0.503 mole), methanol (1 L), a suspension of Pd/C (10%, 46 g, 20% loading) in methanol (500 ml), and methanol (500 ml) from equipment rinses. A solution of HCl in ethanol (1.6N, 460 ml, 0.736 mole, 1.5 eq.) was added and the reactor was pressurized with H2 (3 Bar). The reaction mixture was heated to 40° C. and stirred for 3 hours. The reaction mixture was cooled to 20° C. and flushed with N2. The catalyst was filtered off and washed with methanol (0.5 L). The filtrates were concentrated under vacuum to a yellow solid. The yield of crude title compound was 198 g (97.5%). A reactor was loaded with crude title compound (190 g, 0.47 mole) and toluene (6.65 L) under N2. The suspension was heated under reflux and toluene (150 ml) was added until all solid dissolved. The solution was stirred for 15 minutes more under reflux and then cooled slowly to 20° C. The suspension was stirred for 1 hour at 20° C. The solid was filtered, washed with toluene (680 ml), and dried at 40° C. under vacuum. The yield of pure anhydrous title compound was 158.5 g (83.4%).

Workup

  1. temperatureThe reaction mixture was cooled to 20° C.
  2. customflushed with N2
  3. filtrationThe catalyst was filtered off
  4. washwashed with methanol (0.5 L)
  5. concentrationThe filtrates were concentrated under vacuum to a yellow solid

Sources & evidence

ORD record
ord-064d211ec282476f9ce9e9d182edc310
Source dataset
uspto-grants-2008_04
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US07354920B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes